{"gene":"AURKB","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":1994,"finding":"IPL1 encodes a protein kinase required for high-fidelity chromosome segregation in budding yeast. Type 1 protein phosphatase (PP1/GLC7) acts in opposition to Ipl1 kinase to ensure proper chromosome segregation: overexpression of GLC7 causes chromosome missegregation in wild-type cells, and glc7-1 mutation can partially suppress ipl1-1, establishing these two enzymes as opposing regulators of chromosome segregation.","method":"Genetic epistasis, dosage suppressor screen, conditional mutant analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic interactions, dosage suppression, replicated across multiple studies","pmids":["8007975","7874197"],"is_preprint":false},{"year":1999,"finding":"Ipl1p (Aurora B ortholog) regulates microtubule binding to kinetochores; kinetochores assembled from ipl1 mutant extracts show altered microtubule binding, and Ipl1p phosphorylates the kinetochore component Ndc10p in vitro. Ipl1p localizes to the mitotic spindle with cell-cycle-regulated levels.","method":"In vitro kinase assay (Ndc10p phosphorylation), kinetochore-microtubule binding assay from ipl1 mutant extracts, immunofluorescence localization","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase assay combined with functional kinetochore binding assay and localization, single lab but multiple orthogonal methods","pmids":["10072382"],"is_preprint":false},{"year":2000,"finding":"Ipl1/Aurora kinase and its genetically interacting phosphatase Glc7/PP1 are responsible for the balance of histone H3 serine 10 phosphorylation during mitosis in S. cerevisiae and C. elegans. Both enzymes are required for H3 phosphorylation and chromosome segregation.","method":"Genetic analysis in S. cerevisiae and C. elegans, phospho-H3 staining, epistasis","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — replicated in two model organisms with multiple orthogonal genetic methods","pmids":["10975519"],"is_preprint":false},{"year":1998,"finding":"AIM-1 (rat Aurora B ortholog) controls entry into cytokinesis during M phase; kinase-negative AIM-1 inhibits cleavage furrow formation without affecting nuclear division. Overexpression of wild-type AIM-1 produces multinuclearity and increased ploidy.","method":"Dominant-negative kinase mutant expression, live cell imaging of cytokinesis, flow cytometry for ploidy","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dominant-negative approach with clear cytokinesis phenotype, single lab","pmids":["9809983"],"is_preprint":false},{"year":1998,"finding":"AIR-2 (C. elegans Aurora B ortholog) is required for polar body extrusion and cytokinesis; RNAi-mediated depletion of AIR-2 results in failed cytokinesis with transient cleavage furrow initiation followed by regression, and mislocalization of midbody microtubule components. AIR-2 localizes to chromosomes during meiosis, moves to midbody microtubules at anaphase, and persists at the cytokinesis remnant.","method":"RNAi knockdown in C. elegans, immunofluorescence localization, live imaging","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean RNAi loss-of-function with defined cellular phenotype plus direct localization, replicated observations in meiosis and mitosis","pmids":["9852156"],"is_preprint":false},{"year":1999,"finding":"Sli15 (INCENP ortholog) associates directly with the Ipl1 protein kinase in vivo; both proteins co-localize to the mitotic spindle. sli15 mutant phenotype is very similar to ipl1 mutants and is partially suppressed by reduced PP1 activity, establishing Sli15 as a key functional partner of Ipl1 in chromosome segregation.","method":"Co-immunoprecipitation, genetic epistasis, immunofluorescence","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic and biochemical evidence, co-IP plus epistasis in same study","pmids":["10385519"],"is_preprint":false},{"year":2001,"finding":"Ipl1p (Aurora B) is required to maintain spindle checkpoint arrest induced by lack of tension at kinetochores but is not required for arrest induced by spindle depolymerization. Ipl1p localizes at or near kinetochores during mitosis, distinguishing two mechanistically distinct spindle checkpoint signals.","method":"Genetic analysis, checkpoint arrest assays, immunofluorescence localization","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis dissecting two checkpoint pathways, localization data, single lab with multiple approaches","pmids":["11731476"],"is_preprint":false},{"year":2001,"finding":"The Ipl1-Sli15 complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. In ipl1 mutants, kinetochores remain attached to old spindle pole bodies and fail to turn over attachments, suggesting Ipl1-Sli15 facilitates bi-orientation by promoting turnover of kinetochore-microtubule connections until tension is established.","method":"Live-cell imaging in spindle pole body duplication assay, genetic analysis","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct live imaging of kinetochore attachment dynamics in ipl1 mutants, replicated findings","pmids":["11853667"],"is_preprint":false},{"year":2001,"finding":"Sli15 stimulates the in vitro kinase activity of Ipl1 and facilitates Ipl1's association with the mitotic spindle. Both Ipl1 and Sli15 bind Dam1 (a microtubule-binding kinetochore protein) directly, and Ipl1 phosphorylates both Sli15 and Dam1 in vitro with reduced in vivo phosphorylation in ipl1 mutants. Sli15 and Ipl1 also bind microtubules directly in vitro and are associated with yeast centromeric DNA in vivo.","method":"In vitro kinase assay, Co-immunoprecipitation, microtubule binding assay, chromatin immunoprecipitation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal in vitro and in vivo biochemical methods, replicated across labs","pmids":["11724818"],"is_preprint":false},{"year":2003,"finding":"Ipl1p has a role in mitotic spindle disassembly separable from its chromosome segregation functions. Ipl1-GFP transfers from kinetochores to the spindle after metaphase and accumulates at the spindle midzone late in anaphase; Ipl1p kinase activity increases at anaphase, and ipl1 mutants can stabilize fragile spindles.","method":"Time-lapse microscopy, GFP-tagging, kinase activity assays","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct live imaging with functional phenotype, single lab","pmids":["12566427"],"is_preprint":false},{"year":2005,"finding":"Ipl1/Aurora activates the spindle checkpoint in response to tension defects by creating unattached kinetochores. When Ipl1 function was impaired in kinetochore mutants that appear to have unattached kinetochores, microtubule attachments were restored and the checkpoint was turned off, demonstrating that Ipl1 converts tension defects into unattached kinetochore signals.","method":"Chemical-genetic (analog-sensitive allele), spindle checkpoint assays, kinetochore attachment assays","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — analog-sensitive kinase approach with multiple epistatic tests, rigorous mechanistic dissection","pmids":["16327780"],"is_preprint":false},{"year":2005,"finding":"The Set1 methyltransferase modulates the Ipl1/Glc7 balance. Set1 methylates conserved lysines in the kinetochore protein Dam1, and Dam1 methylation inhibits Ipl1-mediated phosphorylation of flanking serines, demonstrating antagonism between lysine methylation and serine phosphorylation as a mechanism controlling Ipl1 substrate activity.","method":"Genetic epistasis, in vitro kinase assays, biochemical methylation assays","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — biochemical reconstitution of methylation-phosphorylation antagonism plus rigorous genetic epistasis","pmids":["16143104"],"is_preprint":false},{"year":2006,"finding":"Glc7/PP1 ensures accurate chromosome segregation by dephosphorylating Ipl1 targets (particularly Dam1) rather than by regulating Ipl1 kinase levels or activity. Regulatory subunits Gip3 and Gip4 suppress ipl1-321 by redistributing Glc7 away from Ipl1 targets, restoring the balance of Dam1 phosphorylation.","method":"Phosphorylation assays, localization studies, dosage suppressor screen, genetic epistasis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — mechanistic dissection distinguishing phosphatase regulation of substrate vs kinase, multiple orthogonal experiments","pmids":["16537909"],"is_preprint":false},{"year":2007,"finding":"Aurora B kinase (Ipl1) in yeast is essential for protection of meiotic centromeric cohesion. Sgo1 recruits Ipl1 to centromeric regions, and in the absence of Ipl1, the PP2A regulatory subunit Rts1 cannot be maintained at centromeres after anaphase I onset, leading to loss of cohesion protection.","method":"Genetic analysis, localization studies, immunofluorescence","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization evidence plus genetic epistasis, single lab","pmids":["17371833"],"is_preprint":false},{"year":2007,"finding":"Ipl1/Aurora kinase is required for centrosome-mediated spindle assembly in the absence of BimC motor Cin8. Ipl1 regulates Ase1 (spindle midzone protein) by phosphorylating it; an Ase1 mutant lacking Ipl1 consensus phosphorylation sites cannot assemble spindles in the absence of Cin8, and Ase1 phosphorylation and localization are altered in ipl1 mutants.","method":"Genetic epistasis, phosphorylation site mutagenesis, spindle assembly assays, fluorescence microscopy","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — phosphorylation site mutagenesis plus functional rescue experiments, single lab with multiple orthogonal methods","pmids":["17765685"],"is_preprint":false},{"year":2009,"finding":"AURKB phosphorylates H3 at prophase, and RNAi knockdown of AURKB causes mitotic retention of XIST RNA on the inactive X chromosome, demonstrating that AURKB-mediated H3 phosphorylation regulates RNA binding to heterochromatin during mitosis. H3S10 phosphorylation (but not H3S28ph) is excluded from the inactive X and potentially linked to ubiquitination.","method":"RNAi knockdown, pharmacological inhibition, immunofluorescence, RNA-FISH","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi knockdown with specific cellular phenotype (XIST retention), multiple inhibitor controls, single lab","pmids":["19704020"],"is_preprint":false},{"year":2009,"finding":"Ipl1-dependent phosphorylation of the kinetochore protein Dam1 is maximal during S phase and minimal during metaphase; when tension at kinetochores is reduced by failure to establish sister chromatid cohesion, Dam1 phosphorylation persists in metaphase, indicating that tension leads to dephosphorylation of Ipl1 substrates, stabilizing bi-orientation.","method":"Phospho-specific antibodies, genetic manipulation of tension, cell cycle synchronization","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct phosphorylation measurements correlated with tension status, multiple experimental conditions, mechanistically informative","pmids":["19923271"],"is_preprint":false},{"year":2009,"finding":"Phosphorylation of the Ndc80 kinetochore protein by Ipl1/Aurora B reduces its microtubule binding activity in vitro, and kinetochore-bound Ndc80 is phosphorylated on Ipl1 sites in vivo; however, this phosphorylation is not essential alone, indicating additional Ipl1 targets contribute to segregation and checkpoint signaling.","method":"In vitro microtubule binding assay with phosphorylation, in vivo phosphorylation analysis, genetic analysis","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro reconstitution of phosphorylation-dependent microtubule binding, single lab","pmids":["19822728"],"is_preprint":false},{"year":2009,"finding":"Nbl1p is a new core component of the chromosomal passenger complex (CPC) in budding yeast, related to Borealin/Dasra. Nbl1p colocalizes and co-purifies with the CPC (Ipl1/Aurora B, Sli15/INCENP, Bir1/Survivin), is essential for CPC localization, stability, integrity, and function. Structure modeling revealed structural conservation of the CPC architecture from Fungi to Animalia.","method":"Co-purification, co-localization, genetic analysis, comparative structural modeling","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — biochemical co-purification plus functional genetic analysis plus structural modeling, single lab with multiple orthogonal methods","pmids":["19158380"],"is_preprint":false},{"year":2009,"finding":"Ipl1/Aurora B coordinates synaptonemal complex (SC) disassembly with cell cycle progression in budding yeast meiosis. Ipl1 mutants fail to dissociate the central element Zip1 and its binding partner Smt3/SUMO from chromosomes in a timely fashion, and SC disassembly delay occurs even in cdc5 or NDT80-regulated backgrounds.","method":"Genetic analysis, immunofluorescence, meiotic progression assays","journal":"Genes & development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined SC disassembly phenotype, single lab","pmids":["19759266"],"is_preprint":false},{"year":2011,"finding":"Ipl1/Aurora B-dependent phosphorylation of Sli15/INCENP modulates microtubule dynamics by preventing CPC binding to the preanaphase spindle and to the central spindle until late anaphase. Decreased Ipl1-dependent Sli15 phosphorylation drives direct CPC-microtubule binding, revealing how CPC influences microtubule dynamics. Cdk1 and Ipl1/Aurora cooperatively modulate microtubule dynamics.","method":"Phosphorylation site mutagenesis, live-cell imaging, microtubule dynamics assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — phosphorylation site mutagenesis with functional rescue, live imaging, mechanistic reconstitution, single lab multiple orthogonal methods","pmids":["21727193"],"is_preprint":false},{"year":2011,"finding":"Aurora kinase Ipl1 is necessary for maintenance of tight association (cohesion) between duplicated spindle pole bodies (SPBs) during meiosis. Loss of Ipl1 leads to premature SPB separation, overduplication, and multipolar spindles. The Polo-like kinase Cdc5 interacts antagonistically with Ipl1 at the meiotic SPB.","method":"Genetic analysis, fluorescence microscopy, SPB localization assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined SPB phenotype plus antagonistic interaction mapping, single lab","pmids":["21878496"],"is_preprint":false},{"year":2012,"finding":"Cdk1 directly phosphorylates Ipl1/Aurora B on two serine residues in the N-terminal domain, suppressing its association with the microtubule plus-end tracking protein Bim1 until anaphase onset. Failure to phosphorylate Ipl1 leads to premature targeting to the metaphase spindle and constitutive Bim1 phosphorylation, and the non-phosphorylatable Ipl1-Sli15 complex causes severe growth defects.","method":"In vitro kinase assay, phosphorylation site mutagenesis, localization studies, genetic analysis","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro phosphorylation combined with site mutagenesis and functional phenotypic analysis, single lab with multiple orthogonal methods","pmids":["22521784"],"is_preprint":false},{"year":2013,"finding":"Ipl1/Aurora B releases kinetochore-microtubule associations after meiotic entry, liberating chromosomes for homologous pairing in meiosis I. Ipl1 also releases improper kMT connections established early in meiosis, while Mps1 triggers formation of new force-generating attachments, establishing a sequential kinase mechanism for correct chromosome orientation.","method":"Live-cell imaging, chemical genetic inhibition of Ipl1 and Mps1, fluorescence microscopy","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct live imaging of kinetochore dynamics combined with kinase inhibition, rigorous dissection of two kinase activities","pmids":["23371552"],"is_preprint":false},{"year":2014,"finding":"Ipl1/Aurora B-dependent phosphorylation of Sli15 on microtubule-binding domain sites inhibits Sli15-microtubule interaction in vitro; mimicking constitutive phosphorylation delocalizes the CPC in metaphase, while blocking phosphorylation drives excessive spindle localization. These Ipl1-phosphorylation events also regulate the tension checkpoint mechanism.","method":"Phosphorylation site mutagenesis, in vitro microtubule binding assay, in vivo localization studies, checkpoint assay","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro reconstitution of phosphorylation-dependent microtubule binding plus in vivo localization and checkpoint data, multiple orthogonal methods","pmids":["24558497"],"is_preprint":false},{"year":2014,"finding":"Shugoshin (Sgo1) in budding yeast maintains Aurora B/Ipl1 localization on kinetochores during metaphase and also recruits condensin to centromeric chromatin via PP2A-Rts1, demonstrating a dual function of shugoshin in promoting biorientation.","method":"Genetic analysis, localization studies, immunofluorescence","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — localization and genetic epistasis, single lab","pmids":["24945276"],"is_preprint":false},{"year":2015,"finding":"Ipl1/Aurora B is necessary for kinetochore restructuring in meiosis I. Upon meiotic entry, the Ndc80 outer kinetochore complex (but not other subcomplexes) is shed from kinetochores in an Ipl1-dependent manner, promoting assembly of a meiosis-specific kinetochore that confers correct segregation patterns.","method":"Quantitative mass spectrometry of kinetochore components, imaging, genetic analysis","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — quantitative proteomics plus imaging and genetic analysis, mechanistically rigorous","pmids":["26157162"],"is_preprint":false},{"year":2016,"finding":"Aurora B (Aurkb) phosphorylates Oct4 at serine 229 during G2/M, leading to dissociation of Oct4 from chromatin in embryonic stem cells (ESCs). PP1 then binds Oct4 and dephosphorylates S229 during M/G1 transition, resetting Oct4-driven transcription for pluripotency and cell cycle genes. Phospho-mimetic and PP1-binding-deficient Oct4 mutations alter the cell cycle and cause loss of pluripotency.","method":"In vitro kinase assay, phosphorylation site mutagenesis, chromatin binding assays, ESC functional assays","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro kinase assay plus mutagenesis plus functional ESC phenotype, multiple orthogonal methods, single lab","pmids":["26880562"],"is_preprint":false},{"year":2017,"finding":"Rad52 is a substrate of Ipl1/Aurora B kinase in yeast and humans (confirmed by in vitro kinase assay). Ipl1-dependent phosphorylation of Rad52 facilitates kinetochore accumulation of Mps1, linking Aurora B activity to spindle assembly checkpoint regulation via Rad52.","method":"In vitro kinase assay, kinetochore localization assays, genetic epistasis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase assay confirmed substrate, functional localization consequence, single lab","pmids":["29078282"],"is_preprint":false},{"year":2017,"finding":"Phosphorylation of Dam1 by Ipl1/Aurora B kinase at three key serine residues in vivo promotes chromosome bipolar attachment. Phospho-deficient dam1-3A mutants show stabilized kinetochore-microtubule attachment, delay establishment of bipolar attachment after nocodazole washout, and exhibit dramatic chromosome missegregation.","method":"Phospho-deficient mutant analysis in vivo, chromosome segregation assays, spindle checkpoint assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo phospho-mutant analysis with defined phenotype, single lab","pmids":["28928489"],"is_preprint":false},{"year":2018,"finding":"AURKB (Aurora B) phosphorylates survivin, and PLK1 also phosphorylates survivin at different sites to affect cell proliferation. AURKB and PLK1 are required for growth of African American but not European American triple-negative breast cancer (TNBC) xenografts, establishing a context-specific requirement for this phosphorylation axis.","method":"Kinase assays, xenograft tumor models, pharmacological inhibition (barasertib, volasertib), siRNA knockdown","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional experiments including in vivo xenografts and inhibitor treatment, single lab","pmids":["36627281"],"is_preprint":false},{"year":2018,"finding":"VRK1 and AURKB form a stable protein complex; each kinase inhibits the kinase activity of the other and inhibits their respective histone H3 phosphorylations (Thr3 by VRK1, Ser10 by AURKB). Depletion of VRK1 downregulates survivin (BIRC5), preventing AURKB recruitment and localization to centromeres.","method":"Co-immunoprecipitation, in vitro kinase inhibition assays, RNAi knockdown, immunofluorescence","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus in vitro kinase assays with cross-inhibition, single lab, multiple methods","pmids":["29340707"],"is_preprint":false},{"year":2018,"finding":"In mouse oocyte meiosis, AURKC is the predominant CPC kinase. In the absence of AURKC, AURKA localizes to chromosomes in a CPC-dependent manner, suggesting AURKC prevents AURKA from competing for CPC binding. AURKB negatively regulates AURKC to prevent aneuploidy, revealing inter-kinase regulation critical for meiosis.","method":"Single and double knockout mouse models, immunofluorescence localization, oocyte functional assays","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic double knockout with direct localization experiments and functional phenotypes, single lab with multiple orthogonal methods","pmids":["30415701"],"is_preprint":false},{"year":2019,"finding":"AURKB phosphorylates histone H3 at serine 10 (H3S10ph), and this activity activates CCND1 expression through H3S10ph at the CCND1 gene promoter in gastric cancer cells. AZD1152 (AURKB inhibitor) suppresses CCND1 expression and inhibits cell proliferation in vitro and in vivo.","method":"Chromatin immunoprecipitation (ChIP) at CCND1 promoter, AURKB knockdown/inhibitor treatment, proliferation assays, xenograft models","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-based mechanistic evidence for promoter H3S10ph by AURKB plus functional consequences, single lab","pmids":["31982864"],"is_preprint":false},{"year":2019,"finding":"AURKB restrains glucocorticoid (GC) signaling in B-ALL by phosphorylating the histone methyltransferases EHMT1/EHMT2, which are required for GC-induced cell death gene expression. AURKB inhibition enhances GC-induced expression of cell death genes and potentiates GC cytotoxicity in relapsed B-ALL cells.","method":"Genome-wide shRNA screen, AURKB inhibitor treatment, gene expression analysis, functional cell death assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional genomics screen plus mechanistic inhibitor validation, single lab","pmids":["30733284"],"is_preprint":false},{"year":2019,"finding":"In NSCLC cells with acquired resistance to EGFR TKIs, AURKB is activated (measured as increased phospho-histone H3), and AURKB inhibition reduces pH3 levels, triggering G1/S arrest and polyploidy followed by cell death or senescence depending on mutation status.","method":"AURKB inhibitor treatment (barasertib, S49076), phospho-H3 measurement, flow cytometry, cell death assays","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — inhibitor-based functional experiments with defined molecular readout, single lab","pmids":["31000705"],"is_preprint":false},{"year":2019,"finding":"In KSHV-infected tumor cells, the viral latent antigen LANA cleaves AURKB at Asp76 in a serine protease-dependent manner, generating an N'-AURKB isoform that relocalizes to the spindle pole and promotes metaphase-to-telophase transition, enhancing colony formation and malignant growth.","method":"Mass spectrometry identification of cleavage site, mutagenesis, localization studies (immunofluorescence), in vitro/in vivo tumor growth assays","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — protease cleavage site identified biochemically with functional consequence demonstrated in cell and xenograft models, single lab","pmids":["30917319"],"is_preprint":false},{"year":2019,"finding":"COMA complex (Ctf19/Ame1/Okp1/Mcm21) recruits the Sli15/Ipl1 (INCENP/Aurora B) CPC to the inner kinetochore in budding yeast. The Ctf19 C-terminus interacts with the CPC in vitro, and tethering Sli15 to Ame1/Okp1 rescues lethality from Ctf19 depletion in a Sli15 centromere-targeting deficient mutant. Ame1/Okp1 selectively binds Cse4/CENP-A nucleosomes through the Cse4 N-terminus.","method":"Crosslink-guided in vitro reconstitution, Co-IP, genetic rescue experiments","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro reconstitution plus genetic rescue experiments with defined mechanistic outcome, single lab multiple orthogonal methods","pmids":["31112132"],"is_preprint":false},{"year":2020,"finding":"CCAT2 lncRNA interacts directly with and stabilizes BOP1, and BOP1 overexpression promotes chromosomal instability by increasing the active form of Aurora kinase B (AURKB), which regulates chromosomal segregation.","method":"MS2 pull-down, RNA immunoprecipitation, mass spectrometry, CIN assays","journal":"Gastroenterology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA-protein interaction demonstrated with multiple biochemical methods, functional consequence on AURKB activity shown, single lab","pmids":["32805281"],"is_preprint":false},{"year":2021,"finding":"BRAF(V600E) induces mitotic arrest in human melanocytes through microRNA-mediated suppression of AURKB. MIR211-5p and MIR328-3p target AURKB mRNA and their overexpression induces mitotic failure, genome duplication, and proliferation arrest. AURKB expression rescues arrested nevus cells from this arrest.","method":"miRNA overexpression, luciferase reporter assay for AURKB targeting, AURKB rescue experiment, flow cytometry for ploidy","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct miRNA targeting validated with reporter assay plus AURKB rescue experiment, single lab","pmids":["34812139"],"is_preprint":false},{"year":2022,"finding":"Haspin kinase activity is required for recruitment of Aurora B (AURKB) and kinesin MCAK to meiotic centromeres during male meiosis in mice. Haspin inhibition or genetic ablation reduces H3T3 phosphorylation, impairs AURKB centromere localization, and causes chromosome congression defects.","method":"Chemical inhibition (LDN-192960), Haspin-/- mouse model, immunofluorescence of spermatocytes","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — both pharmacological and genetic loss-of-function with direct localization evidence, single lab","pmids":["35694956"],"is_preprint":false},{"year":2022,"finding":"USP29 deubiquitinase stabilizes AURKB by suppressing K48-linked polyubiquitination. FUBP1 transcription factor directly activates USP29 gene transcription, constituting a FUBP1-USP29-AURKB regulatory axis promoting gastric cancer. Systemic knockout of Usp29 in mice reduces AURKB levels in forestomach tissues.","method":"Co-immunoprecipitation, ubiquitination assay, ChIP, luciferase reporter assay, USP29 knockout mice, mass spectrometry","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical ubiquitination assay plus in vivo mouse model, multiple orthogonal methods, single lab","pmids":["38233848"],"is_preprint":false},{"year":2023,"finding":"AURKB inhibition (hesperadin) in uveal melanoma reduces H3S10 phosphorylation at the TERT (telomerase reverse transcriptase) promoter, leading to H3K9 methylation and chromatin condensation that silences TERT transcription, demonstrating an epigenetic mechanism by which AURKB controls telomerase expression.","method":"Chromatin immunoprecipitation (ChIP), RNA-seq, AURKB inhibitor treatment, in vitro/in vivo tumor models","journal":"Investigative ophthalmology & visual science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP mechanistic evidence for AURKB-mediated H3S10ph at a specific promoter, single lab with multiple methods","pmids":["37079315"],"is_preprint":false},{"year":2024,"finding":"AURKB interacts with and modulates the expression of MAD2L2 in bladder cancer cells. AURKB activates MAD2L2 expression to downregulate the p53 DNA damage response pathway, promoting cancer cell proliferation and cell cycle progression. MAD2L2 overexpression rescues AURKB knockdown phenotypes in vitro and in vivo.","method":"Co-immunoprecipitation, Western blot, CRISPR knockdown, xenograft rescue experiments","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional rescue experiments in vitro and in vivo, single lab","pmids":["38515112"],"is_preprint":false},{"year":2024,"finding":"AURKB activates CCNE1 (cyclin E1) expression by phosphorylating histone H3 at serine 10 (H3S10ph) at the CCNE1 promoter in colorectal cancer cells, promoting cell proliferation and tumor growth.","method":"Chromatin immunoprecipitation (ChIP) at CCNE1 promoter, AURKB knockdown/inhibitor (AZD1152), xenograft models","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP mechanistic evidence for AURKB-mediated H3S10ph at a specific promoter, single lab","pmids":["38713155"],"is_preprint":false},{"year":2024,"finding":"AURKB interacts with and phosphorylates DHX9 (DExH-Box helicase 9), targeting its expression in hepatocellular carcinoma cells, and this AURKB-DHX9 interaction promotes HCC progression through the PI3K/AKT/mTOR pathway.","method":"Co-immunoprecipitation, Western blot, functional knockdown and rescue experiments","journal":"Molecular carcinogenesis","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP demonstrating interaction, single lab, limited mechanistic follow-up in the abstract","pmids":["38874176"],"is_preprint":false},{"year":2025,"finding":"AURKB exerts a kinase-independent oncogenic function in colorectal cancer by binding HNRNPM and interfering with its interaction with PSAT1 mRNA, thereby suppressing HNRNPM-mediated mRNA degradation and increasing PSAT1 protein levels. AURKB transcription in CRC is driven by H3K18 lactylation at its promoter.","method":"Mass spectrometry, Co-IP, proximity ligation assay, RNA immunoprecipitation, mRNA stability assay, ChIP-qPCR","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal biochemical methods identifying a kinase-independent protein-RNA regulatory mechanism, single lab","pmids":["40784984"],"is_preprint":false}],"current_model":"AURKB (Aurora B kinase) is the catalytic subunit of the evolutionarily conserved chromosomal passenger complex (CPC; with INCENP/Sli15, Survivin/Bir1, and Borealin/Nbl1), where it phosphorylates histone H3 at serine 10, kinetochore substrates (including Dam1/DASH complex members and Ndc80) to destabilize improper kinetochore-microtubule attachments and promote chromosome bi-orientation, activates the spindle assembly checkpoint by converting tension defects into unattached kinetochore signals, regulates cytokinesis, spindle disassembly, and meiotic chromosome remodeling, and also functions in interphase contexts by epigenetically activating or silencing gene expression through promoter H3S10 phosphorylation; its activity is spatiotemporally controlled by Cdk1-mediated phosphorylation of Ipl1 itself and of INCENP, by opposing PP1/Glc7 phosphatase activity on its substrates, and by upstream regulators including haspin kinase (via H3T3ph), USP29-mediated deubiquitination, and VRK1 cross-inhibition."},"narrative":{"mechanistic_narrative":"AURKB (Aurora B kinase, the IPL1/AIR-2/AIM-1 ortholog) is the catalytic engine of high-fidelity chromosome segregation, functioning as the kinase subunit of the chromosomal passenger complex (CPC) together with INCENP/Sli15, Survivin/Bir1, and Borealin/Nbl1, which together control CPC localization, stability, and activity [PMID:8007975, PMID:7874197, PMID:10385519, PMID:19158380]. Its kinase activity is stimulated by direct association with INCENP/Sli15, which also targets it to the mitotic spindle [PMID:10385519, PMID:11724818]. AURKB enforces chromosome bi-orientation by phosphorylating outer-kinetochore and microtubule-binding substrates — Ndc10, the Dam1/DASH complex, and Ndc80 — to weaken improper kinetochore-microtubule attachments and promote their turnover until tension is established, at which point substrate dephosphorylation by the opposing PP1/Glc7 phosphatase stabilizes correct attachments [PMID:10072382, PMID:11724818, PMID:19923271, PMID:19822728, PMID:28928489, PMID:16537909]. By converting tension defects into unattached-kinetochore signals it activates the spindle assembly checkpoint specifically in response to loss of tension [PMID:11731476, PMID:16327780]. AURKB also phosphorylates histone H3 on serine 10 during mitosis [PMID:10975519, PMID:19704020], and drives cytokinesis, spindle midzone organization, and spindle disassembly through phosphorylation of midzone regulators such as Ase1 and through CPC relocalization to the central spindle [PMID:9809983, PMID:9852156, PMID:12566427, PMID:17765685]. Its spatiotemporal control is layered: Cdk1 phosphorylates AURKB and INCENP/Sli15 to restrain premature spindle binding until anaphase [PMID:21727193, PMID:22521784], haspin-generated H3T3ph and Shugoshin recruit it to centromeres [PMID:35694956, PMID:24945276], USP29-mediated deubiquitination stabilizes it [PMID:38233848], and VRK1 cross-inhibition modulates its H3 phosphorylation [PMID:29340707]. In specialized and disease contexts AURKB remodels meiotic kinetochores and protects meiotic cohesion [PMID:17371833, PMID:23371552, PMID:26157162], resets Oct4-driven pluripotency transcription in stem cells [PMID:26880562], and acts in interphase as a transcriptional regulator by depositing promoter H3S10ph at genes including CCND1, CCNE1, and TERT [PMID:31982864, PMID:38713155, PMID:37079315].","teleology":[{"year":1994,"claim":"Established that a kinase activity opposed by a phosphatase governs chromosome segregation fidelity, defining the foundational kinase-phosphatase balance later shown to act on Aurora B substrates.","evidence":"Genetic epistasis and dosage suppressor screens in budding yeast linking IPL1 and GLC7/PP1","pmids":["8007975","7874197"],"confidence":"High","gaps":["Did not identify direct substrates of the kinase","Mechanism of opposition (substrate vs kinase regulation) unresolved"]},{"year":1998,"claim":"Showed the kinase controls cytokinesis distinct from nuclear division, separating its cleavage-furrow role from chromosome functions.","evidence":"Dominant-negative AIM-1 expression and RNAi of AIR-2 with live imaging of cytokinesis in rat cells and C. elegans","pmids":["9809983","9852156"],"confidence":"High","gaps":["Cytokinesis substrates not identified","Mechanism of midbody relocalization unknown"]},{"year":1999,"claim":"Connected the kinase mechanistically to kinetochores by identifying a direct kinetochore substrate and a stable activating partner.","evidence":"In vitro kinase assay on Ndc10p, kinetochore-microtubule binding from mutant extracts, and Co-IP/epistasis identifying Sli15/INCENP","pmids":["10072382","10385519"],"confidence":"High","gaps":["Did not establish how phosphorylation alters attachment","Full CPC composition not yet defined"]},{"year":2000,"claim":"Identified histone H3 serine 10 as a conserved mitotic substrate balanced by the opposing phosphatase, generalizing the kinase-phosphatase axis to chromatin.","evidence":"Genetic analysis and phospho-H3 staining in S. cerevisiae and C. elegans","pmids":["10975519"],"confidence":"High","gaps":["Functional consequence of H3S10ph for segregation not resolved","Direct vs indirect phosphorylation in vivo not separated here"]},{"year":2001,"claim":"Defined the kinase as the agent of bi-orientation and tension-sensing, distinguishing tension defects from attachment defects in checkpoint signaling.","evidence":"Live imaging of kinetochore attachment turnover, checkpoint arrest assays, and in vitro kinase/microtubule-binding assays on Sli15 and Dam1","pmids":["11731476","11853667","11724818"],"confidence":"High","gaps":["Did not show how tension is read mechanically","Relative contribution of individual substrates unquantified"]},{"year":2005,"claim":"Demonstrated directly that the kinase generates the checkpoint signal by converting tensionless attachments into unattached kinetochores, and uncovered methylation antagonism as a substrate-level control.","evidence":"Analog-sensitive kinase allele with checkpoint and attachment assays; in vitro Set1 methylation inhibiting Dam1 phosphorylation","pmids":["16327780","16143104"],"confidence":"High","gaps":["Physical basis of detachment after phosphorylation not fully defined","Generality of methyl-phospho switch to other substrates unknown"]},{"year":2006,"claim":"Resolved that the opposing phosphatase acts on the kinase's substrates rather than on the kinase itself, clarifying the directionality of the regulatory balance.","evidence":"Phosphorylation assays, localization, and dosage suppressor genetics on Glc7/PP1 regulatory subunits Gip3/Gip4 and Dam1","pmids":["16537909"],"confidence":"High","gaps":["Spatial coordination of phosphatase targeting incompletely mapped"]},{"year":2007,"claim":"Extended kinase function to meiotic cohesion protection and centrosome-driven spindle assembly through new substrates and recruitment factors.","evidence":"Genetic/localization analysis of Sgo1-dependent recruitment and PP2A-Rts1 maintenance; phospho-site mutagenesis of the midzone protein Ase1","pmids":["17371833","17765685"],"confidence":"High","gaps":["Direct phosphorylation of cohesion machinery not shown","Ase1 role outside Cin8-deficient context unclear"]},{"year":2009,"claim":"Built the mechanistic detail of substrate regulation by tension and added core CPC subunit Nbl1, while extending the kinase to mitotic chromatin RNA control and meiotic SC disassembly.","evidence":"Phospho-specific antibodies tracking Dam1/Ndc80 phosphorylation vs tension, Co-purification of Nbl1, RNAi/imaging of XIST retention, and meiotic SC disassembly genetics","pmids":["19923271","19158380","19704020","19822728","19759266"],"confidence":"High","gaps":["Why single-substrate phospho-mutants are insufficient remains open","Mechanism linking H3 phosphorylation to RNA retention not defined"]},{"year":2012,"claim":"Established Cdk1 as a direct upstream regulator that times CPC spindle binding, integrating Aurora B into the mitotic kinase network.","evidence":"In vitro kinase assay, phospho-site mutagenesis, and localization of Cdk1-phosphorylated Sli15/Ipl1 controlling Bim1 association","pmids":["21727193","22521784"],"confidence":"High","gaps":["Coordination with phosphatase counteraction at anaphase not fully resolved"]},{"year":2015,"claim":"Showed the kinase remodels kinetochores and orchestrates attachment release for meiosis, defining a meiosis-specific structural role.","evidence":"Live imaging with chemical-genetic kinase inhibition and quantitative mass spectrometry showing Ipl1-dependent Ndc80 shedding in meiosis I","pmids":["23371552","26157162"],"confidence":"High","gaps":["Substrate driving Ndc80 shedding not pinpointed","Sequential kinase handoff mechanism with Mps1 incompletely mapped"]},{"year":2018,"claim":"Expanded the regulatory network upstream and laterally — VRK1 cross-inhibition, haspin-dependent centromere recruitment, and inter-Aurora kinase regulation in meiosis.","evidence":"Co-IP and reciprocal in vitro kinase inhibition (VRK1); haspin inhibitor/knockout localization in spermatocytes; double-knockout mouse oocyte genetics (AURKB/AURKC)","pmids":["29340707","35694956","30415701"],"confidence":"High","gaps":["Quantitative balance among recruitment inputs unresolved","Tissue specificity of inter-kinase regulation not generalized"]},{"year":2019,"claim":"Defined an interphase transcriptional function in which promoter H3S10ph activates growth genes, and positioned AURKB as a context-dependent therapeutic target.","evidence":"ChIP of H3S10ph at CCND1, EHMT phosphorylation in B-ALL, and inhibitor studies in NSCLC, TNBC, and KSHV cleavage models","pmids":["31982864","30733284","31000705","36627281","30917319"],"confidence":"Medium","gaps":["Direct vs recruited H3S10ph at specific promoters not always separated","Generality of transcriptional roles beyond surveyed cancers unknown"]},{"year":2022,"claim":"Identified post-translational stabilization controlling AURKB abundance, linking deubiquitination to oncogenic signaling.","evidence":"Co-IP, ubiquitination assays, ChIP, and Usp29 knockout mice defining a FUBP1-USP29-AURKB axis","pmids":["38233848"],"confidence":"Medium","gaps":["Whether stabilization affects mitotic vs transcriptional pools unclear"]},{"year":2024,"claim":"Revealed kinase-independent and noncanonical activities, including RNA-binding-protein regulation and additional promoter H3S10ph targets.","evidence":"Co-IP/RNA-IP and mRNA stability assays for HNRNPM/PSAT1 (kinase-independent), DHX9 and MAD2L2 interaction studies, and ChIP at the CCNE1 promoter","pmids":["40784984","38713155","38515112","38874176"],"confidence":"Medium","gaps":["Structural basis of kinase-independent RNA-protein interference unknown","DHX9 interaction rests on Co-IP without reciprocal validation"]},{"year":null,"claim":"How AURKB partitions between its canonical CPC mitotic role and its emerging kinase-independent and interphase transcriptional functions, and how these are coordinately regulated in normal versus malignant cells, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model integrating mitotic and transcriptional pools","Substrate hierarchy across contexts not quantified","Structural determinants of kinase-independent functions undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[1,8,17,27,28,31,45]},{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[2,15,33,44]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[2,15,33,44,42]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[33,44,42,27]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[8,17,24,20]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[46]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2,8,27]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[4,8,13,25]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,5,9,20,24]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[21,36]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[2,15]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,6,7,10,16]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[13,19,23,26,32,40]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[33,44,42,27]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[2,15,11]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[30,34,35,36,41,43,46]}],"complexes":["Chromosomal passenger complex (CPC)"],"partners":["INCENP","BIRC5","BOREALIN/NBL1","DAM1","NDC80","VRK1","USP29","MAD2L2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96GD4","full_name":"Aurora kinase B","aliases":["Aurora 1","Aurora- and IPL1-like midbody-associated protein 1","AIM-1","Aurora/IPL1-related kinase 2","ARK-2","Aurora-related kinase 2","STK-1","Serine/threonine-protein kinase 12","Serine/threonine-protein kinase 5","Serine/threonine-protein kinase aurora-B"],"length_aa":344,"mass_kda":39.3,"function":"Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:29449677). The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:26829474). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (PubMed:15249581). Required for central/midzone spindle assembly and cleavage furrow formation (PubMed:12458200, PubMed:12686604). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (PubMed:11516652, PubMed:12925766, PubMed:14610074). Phosphorylation of INCENP leads to increased AURKB activity (PubMed:11516652, PubMed:12925766, PubMed:14610074). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histones H1.4 and H3 (PubMed:11756469, PubMed:11784863, PubMed:11856369, PubMed:12689593, PubMed:14602875, PubMed:16103226, PubMed:21511733, PubMed:21658950). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (PubMed:21658950). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863, PubMed:11856369). AURKB is also required for kinetochore localization of BUB1 and SGO1 (PubMed:15020684, PubMed:17617734). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (PubMed:20959462). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (PubMed:33542149). Phosphorylates KRT5 during anaphase and telophase (By similarity). Phosphorylates ATXN10 which promotes phosphorylation of ATXN10 by PLK1 and may play a role in the regulation of cytokinesis and stimulating the proteasomal degradation of ATXN10 (PubMed:25666058)","subcellular_location":"Nucleus; Chromosome; Chromosome, centromere; Chromosome, centromere, kinetochore; Cytoplasm, cytoskeleton, spindle; Midbody","url":"https://www.uniprot.org/uniprotkb/Q96GD4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/AURKB","classification":"Common Essential","n_dependent_lines":1204,"n_total_lines":1208,"dependency_fraction":0.9966887417218543},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000178999","cell_line_id":"CID001129","localizations":[{"compartment":"chromatin","grade":3}],"interactors":[{"gene":"INCENP","stoichiometry":0.2},{"gene":"CDCA8","stoichiometry":0.2},{"gene":"CDC37","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001129","total_profiled":1310},"omim":[{"mim_id":"620959","title":"UBIQUITIN-SPECIFIC PEPTIDASE 35; USP35","url":"https://www.omim.org/entry/620959"},{"mim_id":"619635","title":"ZINC FINGER FYVE DOMAIN-CONTAINING PROTEIN 19; ZFYVE19","url":"https://www.omim.org/entry/619635"},{"mim_id":"619403","title":"COLON CANCER-ASSOCIATED TRANSCRIPT 2, NONCODING; CCAT2","url":"https://www.omim.org/entry/619403"},{"mim_id":"619358","title":"MICROTUBULE-ASSOCIATED SCAFFOLD PROTEIN 2; MTUS2","url":"https://www.omim.org/entry/619358"},{"mim_id":"619288","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 69; CCDC69","url":"https://www.omim.org/entry/619288"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Kinetochore","reliability":"Additional"},{"location":"Midbody","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":41.6},{"tissue":"lymphoid tissue","ntpm":55.9}],"url":"https://www.proteinatlas.org/search/AURKB"},"hgnc":{"alias_symbol":["Aik2","IPL1","AurB","AIM-1","ARK2","STK5","PPP1R48"],"prev_symbol":["STK12"]},"alphafold":{"accession":"Q96GD4","domains":[{"cath_id":"3.30.200.20","chopping":"75-156","consensus_level":"high","plddt":92.9759,"start":75,"end":156},{"cath_id":"1.10.510.10","chopping":"161-332","consensus_level":"high","plddt":90.937,"start":161,"end":332}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GD4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GD4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GD4-F1-predicted_aligned_error_v6.png","plddt_mean":78.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=AURKB","jax_strain_url":"https://www.jax.org/strain/search?query=AURKB"},"sequence":{"accession":"Q96GD4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96GD4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96GD4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GD4"}},"corpus_meta":[{"pmid":"10975519","id":"PMC_10975519","title":"Mitotic 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Type 1 protein phosphatase (PP1/GLC7) acts in opposition to Ipl1 kinase to ensure proper chromosome segregation: overexpression of GLC7 causes chromosome missegregation in wild-type cells, and glc7-1 mutation can partially suppress ipl1-1, establishing these two enzymes as opposing regulators of chromosome segregation.\",\n      \"method\": \"Genetic epistasis, dosage suppressor screen, conditional mutant analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic interactions, dosage suppression, replicated across multiple studies\",\n      \"pmids\": [\"8007975\", \"7874197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Ipl1p (Aurora B ortholog) regulates microtubule binding to kinetochores; kinetochores assembled from ipl1 mutant extracts show altered microtubule binding, and Ipl1p phosphorylates the kinetochore component Ndc10p in vitro. Ipl1p localizes to the mitotic spindle with cell-cycle-regulated levels.\",\n      \"method\": \"In vitro kinase assay (Ndc10p phosphorylation), kinetochore-microtubule binding assay from ipl1 mutant extracts, immunofluorescence localization\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase assay combined with functional kinetochore binding assay and localization, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"10072382\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Ipl1/Aurora kinase and its genetically interacting phosphatase Glc7/PP1 are responsible for the balance of histone H3 serine 10 phosphorylation during mitosis in S. cerevisiae and C. elegans. Both enzymes are required for H3 phosphorylation and chromosome segregation.\",\n      \"method\": \"Genetic analysis in S. cerevisiae and C. elegans, phospho-H3 staining, epistasis\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — replicated in two model organisms with multiple orthogonal genetic methods\",\n      \"pmids\": [\"10975519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"AIM-1 (rat Aurora B ortholog) controls entry into cytokinesis during M phase; kinase-negative AIM-1 inhibits cleavage furrow formation without affecting nuclear division. Overexpression of wild-type AIM-1 produces multinuclearity and increased ploidy.\",\n      \"method\": \"Dominant-negative kinase mutant expression, live cell imaging of cytokinesis, flow cytometry for ploidy\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dominant-negative approach with clear cytokinesis phenotype, single lab\",\n      \"pmids\": [\"9809983\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"AIR-2 (C. elegans Aurora B ortholog) is required for polar body extrusion and cytokinesis; RNAi-mediated depletion of AIR-2 results in failed cytokinesis with transient cleavage furrow initiation followed by regression, and mislocalization of midbody microtubule components. AIR-2 localizes to chromosomes during meiosis, moves to midbody microtubules at anaphase, and persists at the cytokinesis remnant.\",\n      \"method\": \"RNAi knockdown in C. elegans, immunofluorescence localization, live imaging\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean RNAi loss-of-function with defined cellular phenotype plus direct localization, replicated observations in meiosis and mitosis\",\n      \"pmids\": [\"9852156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Sli15 (INCENP ortholog) associates directly with the Ipl1 protein kinase in vivo; both proteins co-localize to the mitotic spindle. sli15 mutant phenotype is very similar to ipl1 mutants and is partially suppressed by reduced PP1 activity, establishing Sli15 as a key functional partner of Ipl1 in chromosome segregation.\",\n      \"method\": \"Co-immunoprecipitation, genetic epistasis, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic and biochemical evidence, co-IP plus epistasis in same study\",\n      \"pmids\": [\"10385519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Ipl1p (Aurora B) is required to maintain spindle checkpoint arrest induced by lack of tension at kinetochores but is not required for arrest induced by spindle depolymerization. Ipl1p localizes at or near kinetochores during mitosis, distinguishing two mechanistically distinct spindle checkpoint signals.\",\n      \"method\": \"Genetic analysis, checkpoint arrest assays, immunofluorescence localization\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis dissecting two checkpoint pathways, localization data, single lab with multiple approaches\",\n      \"pmids\": [\"11731476\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"The Ipl1-Sli15 complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. In ipl1 mutants, kinetochores remain attached to old spindle pole bodies and fail to turn over attachments, suggesting Ipl1-Sli15 facilitates bi-orientation by promoting turnover of kinetochore-microtubule connections until tension is established.\",\n      \"method\": \"Live-cell imaging in spindle pole body duplication assay, genetic analysis\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct live imaging of kinetochore attachment dynamics in ipl1 mutants, replicated findings\",\n      \"pmids\": [\"11853667\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Sli15 stimulates the in vitro kinase activity of Ipl1 and facilitates Ipl1's association with the mitotic spindle. Both Ipl1 and Sli15 bind Dam1 (a microtubule-binding kinetochore protein) directly, and Ipl1 phosphorylates both Sli15 and Dam1 in vitro with reduced in vivo phosphorylation in ipl1 mutants. Sli15 and Ipl1 also bind microtubules directly in vitro and are associated with yeast centromeric DNA in vivo.\",\n      \"method\": \"In vitro kinase assay, Co-immunoprecipitation, microtubule binding assay, chromatin immunoprecipitation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal in vitro and in vivo biochemical methods, replicated across labs\",\n      \"pmids\": [\"11724818\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Ipl1p has a role in mitotic spindle disassembly separable from its chromosome segregation functions. Ipl1-GFP transfers from kinetochores to the spindle after metaphase and accumulates at the spindle midzone late in anaphase; Ipl1p kinase activity increases at anaphase, and ipl1 mutants can stabilize fragile spindles.\",\n      \"method\": \"Time-lapse microscopy, GFP-tagging, kinase activity assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct live imaging with functional phenotype, single lab\",\n      \"pmids\": [\"12566427\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Ipl1/Aurora activates the spindle checkpoint in response to tension defects by creating unattached kinetochores. When Ipl1 function was impaired in kinetochore mutants that appear to have unattached kinetochores, microtubule attachments were restored and the checkpoint was turned off, demonstrating that Ipl1 converts tension defects into unattached kinetochore signals.\",\n      \"method\": \"Chemical-genetic (analog-sensitive allele), spindle checkpoint assays, kinetochore attachment assays\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — analog-sensitive kinase approach with multiple epistatic tests, rigorous mechanistic dissection\",\n      \"pmids\": [\"16327780\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The Set1 methyltransferase modulates the Ipl1/Glc7 balance. Set1 methylates conserved lysines in the kinetochore protein Dam1, and Dam1 methylation inhibits Ipl1-mediated phosphorylation of flanking serines, demonstrating antagonism between lysine methylation and serine phosphorylation as a mechanism controlling Ipl1 substrate activity.\",\n      \"method\": \"Genetic epistasis, in vitro kinase assays, biochemical methylation assays\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — biochemical reconstitution of methylation-phosphorylation antagonism plus rigorous genetic epistasis\",\n      \"pmids\": [\"16143104\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Glc7/PP1 ensures accurate chromosome segregation by dephosphorylating Ipl1 targets (particularly Dam1) rather than by regulating Ipl1 kinase levels or activity. Regulatory subunits Gip3 and Gip4 suppress ipl1-321 by redistributing Glc7 away from Ipl1 targets, restoring the balance of Dam1 phosphorylation.\",\n      \"method\": \"Phosphorylation assays, localization studies, dosage suppressor screen, genetic epistasis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mechanistic dissection distinguishing phosphatase regulation of substrate vs kinase, multiple orthogonal experiments\",\n      \"pmids\": [\"16537909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Aurora B kinase (Ipl1) in yeast is essential for protection of meiotic centromeric cohesion. Sgo1 recruits Ipl1 to centromeric regions, and in the absence of Ipl1, the PP2A regulatory subunit Rts1 cannot be maintained at centromeres after anaphase I onset, leading to loss of cohesion protection.\",\n      \"method\": \"Genetic analysis, localization studies, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization evidence plus genetic epistasis, single lab\",\n      \"pmids\": [\"17371833\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Ipl1/Aurora kinase is required for centrosome-mediated spindle assembly in the absence of BimC motor Cin8. Ipl1 regulates Ase1 (spindle midzone protein) by phosphorylating it; an Ase1 mutant lacking Ipl1 consensus phosphorylation sites cannot assemble spindles in the absence of Cin8, and Ase1 phosphorylation and localization are altered in ipl1 mutants.\",\n      \"method\": \"Genetic epistasis, phosphorylation site mutagenesis, spindle assembly assays, fluorescence microscopy\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — phosphorylation site mutagenesis plus functional rescue experiments, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"17765685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"AURKB phosphorylates H3 at prophase, and RNAi knockdown of AURKB causes mitotic retention of XIST RNA on the inactive X chromosome, demonstrating that AURKB-mediated H3 phosphorylation regulates RNA binding to heterochromatin during mitosis. H3S10 phosphorylation (but not H3S28ph) is excluded from the inactive X and potentially linked to ubiquitination.\",\n      \"method\": \"RNAi knockdown, pharmacological inhibition, immunofluorescence, RNA-FISH\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi knockdown with specific cellular phenotype (XIST retention), multiple inhibitor controls, single lab\",\n      \"pmids\": [\"19704020\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Ipl1-dependent phosphorylation of the kinetochore protein Dam1 is maximal during S phase and minimal during metaphase; when tension at kinetochores is reduced by failure to establish sister chromatid cohesion, Dam1 phosphorylation persists in metaphase, indicating that tension leads to dephosphorylation of Ipl1 substrates, stabilizing bi-orientation.\",\n      \"method\": \"Phospho-specific antibodies, genetic manipulation of tension, cell cycle synchronization\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct phosphorylation measurements correlated with tension status, multiple experimental conditions, mechanistically informative\",\n      \"pmids\": [\"19923271\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Phosphorylation of the Ndc80 kinetochore protein by Ipl1/Aurora B reduces its microtubule binding activity in vitro, and kinetochore-bound Ndc80 is phosphorylated on Ipl1 sites in vivo; however, this phosphorylation is not essential alone, indicating additional Ipl1 targets contribute to segregation and checkpoint signaling.\",\n      \"method\": \"In vitro microtubule binding assay with phosphorylation, in vivo phosphorylation analysis, genetic analysis\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro reconstitution of phosphorylation-dependent microtubule binding, single lab\",\n      \"pmids\": [\"19822728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Nbl1p is a new core component of the chromosomal passenger complex (CPC) in budding yeast, related to Borealin/Dasra. Nbl1p colocalizes and co-purifies with the CPC (Ipl1/Aurora B, Sli15/INCENP, Bir1/Survivin), is essential for CPC localization, stability, integrity, and function. Structure modeling revealed structural conservation of the CPC architecture from Fungi to Animalia.\",\n      \"method\": \"Co-purification, co-localization, genetic analysis, comparative structural modeling\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — biochemical co-purification plus functional genetic analysis plus structural modeling, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"19158380\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Ipl1/Aurora B coordinates synaptonemal complex (SC) disassembly with cell cycle progression in budding yeast meiosis. Ipl1 mutants fail to dissociate the central element Zip1 and its binding partner Smt3/SUMO from chromosomes in a timely fashion, and SC disassembly delay occurs even in cdc5 or NDT80-regulated backgrounds.\",\n      \"method\": \"Genetic analysis, immunofluorescence, meiotic progression assays\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined SC disassembly phenotype, single lab\",\n      \"pmids\": [\"19759266\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Ipl1/Aurora B-dependent phosphorylation of Sli15/INCENP modulates microtubule dynamics by preventing CPC binding to the preanaphase spindle and to the central spindle until late anaphase. Decreased Ipl1-dependent Sli15 phosphorylation drives direct CPC-microtubule binding, revealing how CPC influences microtubule dynamics. Cdk1 and Ipl1/Aurora cooperatively modulate microtubule dynamics.\",\n      \"method\": \"Phosphorylation site mutagenesis, live-cell imaging, microtubule dynamics assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — phosphorylation site mutagenesis with functional rescue, live imaging, mechanistic reconstitution, single lab multiple orthogonal methods\",\n      \"pmids\": [\"21727193\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Aurora kinase Ipl1 is necessary for maintenance of tight association (cohesion) between duplicated spindle pole bodies (SPBs) during meiosis. Loss of Ipl1 leads to premature SPB separation, overduplication, and multipolar spindles. The Polo-like kinase Cdc5 interacts antagonistically with Ipl1 at the meiotic SPB.\",\n      \"method\": \"Genetic analysis, fluorescence microscopy, SPB localization assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined SPB phenotype plus antagonistic interaction mapping, single lab\",\n      \"pmids\": [\"21878496\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Cdk1 directly phosphorylates Ipl1/Aurora B on two serine residues in the N-terminal domain, suppressing its association with the microtubule plus-end tracking protein Bim1 until anaphase onset. Failure to phosphorylate Ipl1 leads to premature targeting to the metaphase spindle and constitutive Bim1 phosphorylation, and the non-phosphorylatable Ipl1-Sli15 complex causes severe growth defects.\",\n      \"method\": \"In vitro kinase assay, phosphorylation site mutagenesis, localization studies, genetic analysis\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro phosphorylation combined with site mutagenesis and functional phenotypic analysis, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"22521784\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Ipl1/Aurora B releases kinetochore-microtubule associations after meiotic entry, liberating chromosomes for homologous pairing in meiosis I. Ipl1 also releases improper kMT connections established early in meiosis, while Mps1 triggers formation of new force-generating attachments, establishing a sequential kinase mechanism for correct chromosome orientation.\",\n      \"method\": \"Live-cell imaging, chemical genetic inhibition of Ipl1 and Mps1, fluorescence microscopy\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct live imaging of kinetochore dynamics combined with kinase inhibition, rigorous dissection of two kinase activities\",\n      \"pmids\": [\"23371552\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Ipl1/Aurora B-dependent phosphorylation of Sli15 on microtubule-binding domain sites inhibits Sli15-microtubule interaction in vitro; mimicking constitutive phosphorylation delocalizes the CPC in metaphase, while blocking phosphorylation drives excessive spindle localization. These Ipl1-phosphorylation events also regulate the tension checkpoint mechanism.\",\n      \"method\": \"Phosphorylation site mutagenesis, in vitro microtubule binding assay, in vivo localization studies, checkpoint assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro reconstitution of phosphorylation-dependent microtubule binding plus in vivo localization and checkpoint data, multiple orthogonal methods\",\n      \"pmids\": [\"24558497\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Shugoshin (Sgo1) in budding yeast maintains Aurora B/Ipl1 localization on kinetochores during metaphase and also recruits condensin to centromeric chromatin via PP2A-Rts1, demonstrating a dual function of shugoshin in promoting biorientation.\",\n      \"method\": \"Genetic analysis, localization studies, immunofluorescence\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — localization and genetic epistasis, single lab\",\n      \"pmids\": [\"24945276\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Ipl1/Aurora B is necessary for kinetochore restructuring in meiosis I. Upon meiotic entry, the Ndc80 outer kinetochore complex (but not other subcomplexes) is shed from kinetochores in an Ipl1-dependent manner, promoting assembly of a meiosis-specific kinetochore that confers correct segregation patterns.\",\n      \"method\": \"Quantitative mass spectrometry of kinetochore components, imaging, genetic analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — quantitative proteomics plus imaging and genetic analysis, mechanistically rigorous\",\n      \"pmids\": [\"26157162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Aurora B (Aurkb) phosphorylates Oct4 at serine 229 during G2/M, leading to dissociation of Oct4 from chromatin in embryonic stem cells (ESCs). PP1 then binds Oct4 and dephosphorylates S229 during M/G1 transition, resetting Oct4-driven transcription for pluripotency and cell cycle genes. Phospho-mimetic and PP1-binding-deficient Oct4 mutations alter the cell cycle and cause loss of pluripotency.\",\n      \"method\": \"In vitro kinase assay, phosphorylation site mutagenesis, chromatin binding assays, ESC functional assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro kinase assay plus mutagenesis plus functional ESC phenotype, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"26880562\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Rad52 is a substrate of Ipl1/Aurora B kinase in yeast and humans (confirmed by in vitro kinase assay). Ipl1-dependent phosphorylation of Rad52 facilitates kinetochore accumulation of Mps1, linking Aurora B activity to spindle assembly checkpoint regulation via Rad52.\",\n      \"method\": \"In vitro kinase assay, kinetochore localization assays, genetic epistasis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase assay confirmed substrate, functional localization consequence, single lab\",\n      \"pmids\": [\"29078282\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Phosphorylation of Dam1 by Ipl1/Aurora B kinase at three key serine residues in vivo promotes chromosome bipolar attachment. Phospho-deficient dam1-3A mutants show stabilized kinetochore-microtubule attachment, delay establishment of bipolar attachment after nocodazole washout, and exhibit dramatic chromosome missegregation.\",\n      \"method\": \"Phospho-deficient mutant analysis in vivo, chromosome segregation assays, spindle checkpoint assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo phospho-mutant analysis with defined phenotype, single lab\",\n      \"pmids\": [\"28928489\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"AURKB (Aurora B) phosphorylates survivin, and PLK1 also phosphorylates survivin at different sites to affect cell proliferation. AURKB and PLK1 are required for growth of African American but not European American triple-negative breast cancer (TNBC) xenografts, establishing a context-specific requirement for this phosphorylation axis.\",\n      \"method\": \"Kinase assays, xenograft tumor models, pharmacological inhibition (barasertib, volasertib), siRNA knockdown\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional experiments including in vivo xenografts and inhibitor treatment, single lab\",\n      \"pmids\": [\"36627281\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"VRK1 and AURKB form a stable protein complex; each kinase inhibits the kinase activity of the other and inhibits their respective histone H3 phosphorylations (Thr3 by VRK1, Ser10 by AURKB). Depletion of VRK1 downregulates survivin (BIRC5), preventing AURKB recruitment and localization to centromeres.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase inhibition assays, RNAi knockdown, immunofluorescence\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus in vitro kinase assays with cross-inhibition, single lab, multiple methods\",\n      \"pmids\": [\"29340707\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In mouse oocyte meiosis, AURKC is the predominant CPC kinase. In the absence of AURKC, AURKA localizes to chromosomes in a CPC-dependent manner, suggesting AURKC prevents AURKA from competing for CPC binding. AURKB negatively regulates AURKC to prevent aneuploidy, revealing inter-kinase regulation critical for meiosis.\",\n      \"method\": \"Single and double knockout mouse models, immunofluorescence localization, oocyte functional assays\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic double knockout with direct localization experiments and functional phenotypes, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"30415701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"AURKB phosphorylates histone H3 at serine 10 (H3S10ph), and this activity activates CCND1 expression through H3S10ph at the CCND1 gene promoter in gastric cancer cells. AZD1152 (AURKB inhibitor) suppresses CCND1 expression and inhibits cell proliferation in vitro and in vivo.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP) at CCND1 promoter, AURKB knockdown/inhibitor treatment, proliferation assays, xenograft models\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-based mechanistic evidence for promoter H3S10ph by AURKB plus functional consequences, single lab\",\n      \"pmids\": [\"31982864\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"AURKB restrains glucocorticoid (GC) signaling in B-ALL by phosphorylating the histone methyltransferases EHMT1/EHMT2, which are required for GC-induced cell death gene expression. AURKB inhibition enhances GC-induced expression of cell death genes and potentiates GC cytotoxicity in relapsed B-ALL cells.\",\n      \"method\": \"Genome-wide shRNA screen, AURKB inhibitor treatment, gene expression analysis, functional cell death assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional genomics screen plus mechanistic inhibitor validation, single lab\",\n      \"pmids\": [\"30733284\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In NSCLC cells with acquired resistance to EGFR TKIs, AURKB is activated (measured as increased phospho-histone H3), and AURKB inhibition reduces pH3 levels, triggering G1/S arrest and polyploidy followed by cell death or senescence depending on mutation status.\",\n      \"method\": \"AURKB inhibitor treatment (barasertib, S49076), phospho-H3 measurement, flow cytometry, cell death assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — inhibitor-based functional experiments with defined molecular readout, single lab\",\n      \"pmids\": [\"31000705\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In KSHV-infected tumor cells, the viral latent antigen LANA cleaves AURKB at Asp76 in a serine protease-dependent manner, generating an N'-AURKB isoform that relocalizes to the spindle pole and promotes metaphase-to-telophase transition, enhancing colony formation and malignant growth.\",\n      \"method\": \"Mass spectrometry identification of cleavage site, mutagenesis, localization studies (immunofluorescence), in vitro/in vivo tumor growth assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — protease cleavage site identified biochemically with functional consequence demonstrated in cell and xenograft models, single lab\",\n      \"pmids\": [\"30917319\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"COMA complex (Ctf19/Ame1/Okp1/Mcm21) recruits the Sli15/Ipl1 (INCENP/Aurora B) CPC to the inner kinetochore in budding yeast. The Ctf19 C-terminus interacts with the CPC in vitro, and tethering Sli15 to Ame1/Okp1 rescues lethality from Ctf19 depletion in a Sli15 centromere-targeting deficient mutant. Ame1/Okp1 selectively binds Cse4/CENP-A nucleosomes through the Cse4 N-terminus.\",\n      \"method\": \"Crosslink-guided in vitro reconstitution, Co-IP, genetic rescue experiments\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro reconstitution plus genetic rescue experiments with defined mechanistic outcome, single lab multiple orthogonal methods\",\n      \"pmids\": [\"31112132\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CCAT2 lncRNA interacts directly with and stabilizes BOP1, and BOP1 overexpression promotes chromosomal instability by increasing the active form of Aurora kinase B (AURKB), which regulates chromosomal segregation.\",\n      \"method\": \"MS2 pull-down, RNA immunoprecipitation, mass spectrometry, CIN assays\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA-protein interaction demonstrated with multiple biochemical methods, functional consequence on AURKB activity shown, single lab\",\n      \"pmids\": [\"32805281\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"BRAF(V600E) induces mitotic arrest in human melanocytes through microRNA-mediated suppression of AURKB. MIR211-5p and MIR328-3p target AURKB mRNA and their overexpression induces mitotic failure, genome duplication, and proliferation arrest. AURKB expression rescues arrested nevus cells from this arrest.\",\n      \"method\": \"miRNA overexpression, luciferase reporter assay for AURKB targeting, AURKB rescue experiment, flow cytometry for ploidy\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct miRNA targeting validated with reporter assay plus AURKB rescue experiment, single lab\",\n      \"pmids\": [\"34812139\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Haspin kinase activity is required for recruitment of Aurora B (AURKB) and kinesin MCAK to meiotic centromeres during male meiosis in mice. Haspin inhibition or genetic ablation reduces H3T3 phosphorylation, impairs AURKB centromere localization, and causes chromosome congression defects.\",\n      \"method\": \"Chemical inhibition (LDN-192960), Haspin-/- mouse model, immunofluorescence of spermatocytes\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — both pharmacological and genetic loss-of-function with direct localization evidence, single lab\",\n      \"pmids\": [\"35694956\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"USP29 deubiquitinase stabilizes AURKB by suppressing K48-linked polyubiquitination. FUBP1 transcription factor directly activates USP29 gene transcription, constituting a FUBP1-USP29-AURKB regulatory axis promoting gastric cancer. Systemic knockout of Usp29 in mice reduces AURKB levels in forestomach tissues.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, ChIP, luciferase reporter assay, USP29 knockout mice, mass spectrometry\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical ubiquitination assay plus in vivo mouse model, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"38233848\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"AURKB inhibition (hesperadin) in uveal melanoma reduces H3S10 phosphorylation at the TERT (telomerase reverse transcriptase) promoter, leading to H3K9 methylation and chromatin condensation that silences TERT transcription, demonstrating an epigenetic mechanism by which AURKB controls telomerase expression.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP), RNA-seq, AURKB inhibitor treatment, in vitro/in vivo tumor models\",\n      \"journal\": \"Investigative ophthalmology & visual science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP mechanistic evidence for AURKB-mediated H3S10ph at a specific promoter, single lab with multiple methods\",\n      \"pmids\": [\"37079315\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"AURKB interacts with and modulates the expression of MAD2L2 in bladder cancer cells. AURKB activates MAD2L2 expression to downregulate the p53 DNA damage response pathway, promoting cancer cell proliferation and cell cycle progression. MAD2L2 overexpression rescues AURKB knockdown phenotypes in vitro and in vivo.\",\n      \"method\": \"Co-immunoprecipitation, Western blot, CRISPR knockdown, xenograft rescue experiments\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional rescue experiments in vitro and in vivo, single lab\",\n      \"pmids\": [\"38515112\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"AURKB activates CCNE1 (cyclin E1) expression by phosphorylating histone H3 at serine 10 (H3S10ph) at the CCNE1 promoter in colorectal cancer cells, promoting cell proliferation and tumor growth.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP) at CCNE1 promoter, AURKB knockdown/inhibitor (AZD1152), xenograft models\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP mechanistic evidence for AURKB-mediated H3S10ph at a specific promoter, single lab\",\n      \"pmids\": [\"38713155\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"AURKB interacts with and phosphorylates DHX9 (DExH-Box helicase 9), targeting its expression in hepatocellular carcinoma cells, and this AURKB-DHX9 interaction promotes HCC progression through the PI3K/AKT/mTOR pathway.\",\n      \"method\": \"Co-immunoprecipitation, Western blot, functional knockdown and rescue experiments\",\n      \"journal\": \"Molecular carcinogenesis\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP demonstrating interaction, single lab, limited mechanistic follow-up in the abstract\",\n      \"pmids\": [\"38874176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"AURKB exerts a kinase-independent oncogenic function in colorectal cancer by binding HNRNPM and interfering with its interaction with PSAT1 mRNA, thereby suppressing HNRNPM-mediated mRNA degradation and increasing PSAT1 protein levels. AURKB transcription in CRC is driven by H3K18 lactylation at its promoter.\",\n      \"method\": \"Mass spectrometry, Co-IP, proximity ligation assay, RNA immunoprecipitation, mRNA stability assay, ChIP-qPCR\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal biochemical methods identifying a kinase-independent protein-RNA regulatory mechanism, single lab\",\n      \"pmids\": [\"40784984\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"AURKB (Aurora B kinase) is the catalytic subunit of the evolutionarily conserved chromosomal passenger complex (CPC; with INCENP/Sli15, Survivin/Bir1, and Borealin/Nbl1), where it phosphorylates histone H3 at serine 10, kinetochore substrates (including Dam1/DASH complex members and Ndc80) to destabilize improper kinetochore-microtubule attachments and promote chromosome bi-orientation, activates the spindle assembly checkpoint by converting tension defects into unattached kinetochore signals, regulates cytokinesis, spindle disassembly, and meiotic chromosome remodeling, and also functions in interphase contexts by epigenetically activating or silencing gene expression through promoter H3S10 phosphorylation; its activity is spatiotemporally controlled by Cdk1-mediated phosphorylation of Ipl1 itself and of INCENP, by opposing PP1/Glc7 phosphatase activity on its substrates, and by upstream regulators including haspin kinase (via H3T3ph), USP29-mediated deubiquitination, and VRK1 cross-inhibition.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"AURKB (Aurora B kinase, the IPL1/AIR-2/AIM-1 ortholog) is the catalytic engine of high-fidelity chromosome segregation, functioning as the kinase subunit of the chromosomal passenger complex (CPC) together with INCENP/Sli15, Survivin/Bir1, and Borealin/Nbl1, which together control CPC localization, stability, and activity [#0, #5, #18]. Its kinase activity is stimulated by direct association with INCENP/Sli15, which also targets it to the mitotic spindle [#5, #8]. AURKB enforces chromosome bi-orientation by phosphorylating outer-kinetochore and microtubule-binding substrates — Ndc10, the Dam1/DASH complex, and Ndc80 — to weaken improper kinetochore-microtubule attachments and promote their turnover until tension is established, at which point substrate dephosphorylation by the opposing PP1/Glc7 phosphatase stabilizes correct attachments [#1, #8, #16, #17, #29, #12]. By converting tension defects into unattached-kinetochore signals it activates the spindle assembly checkpoint specifically in response to loss of tension [#6, #10]. AURKB also phosphorylates histone H3 on serine 10 during mitosis [#2, #15], and drives cytokinesis, spindle midzone organization, and spindle disassembly through phosphorylation of midzone regulators such as Ase1 and through CPC relocalization to the central spindle [#3, #4, #9, #14]. Its spatiotemporal control is layered: Cdk1 phosphorylates AURKB and INCENP/Sli15 to restrain premature spindle binding until anaphase [#20, #22], haspin-generated H3T3ph and Shugoshin recruit it to centromeres [#40, #25], USP29-mediated deubiquitination stabilizes it [#41], and VRK1 cross-inhibition modulates its H3 phosphorylation [#31]. In specialized and disease contexts AURKB remodels meiotic kinetochores and protects meiotic cohesion [#13, #23, #26], resets Oct4-driven pluripotency transcription in stem cells [#27], and acts in interphase as a transcriptional regulator by depositing promoter H3S10ph at genes including CCND1, CCNE1, and TERT [#33, #44, #42].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Established that a kinase activity opposed by a phosphatase governs chromosome segregation fidelity, defining the foundational kinase-phosphatase balance later shown to act on Aurora B substrates.\",\n      \"evidence\": \"Genetic epistasis and dosage suppressor screens in budding yeast linking IPL1 and GLC7/PP1\",\n      \"pmids\": [\"8007975\", \"7874197\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify direct substrates of the kinase\", \"Mechanism of opposition (substrate vs kinase regulation) unresolved\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Showed the kinase controls cytokinesis distinct from nuclear division, separating its cleavage-furrow role from chromosome functions.\",\n      \"evidence\": \"Dominant-negative AIM-1 expression and RNAi of AIR-2 with live imaging of cytokinesis in rat cells and C. elegans\",\n      \"pmids\": [\"9809983\", \"9852156\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Cytokinesis substrates not identified\", \"Mechanism of midbody relocalization unknown\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Connected the kinase mechanistically to kinetochores by identifying a direct kinetochore substrate and a stable activating partner.\",\n      \"evidence\": \"In vitro kinase assay on Ndc10p, kinetochore-microtubule binding from mutant extracts, and Co-IP/epistasis identifying Sli15/INCENP\",\n      \"pmids\": [\"10072382\", \"10385519\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not establish how phosphorylation alters attachment\", \"Full CPC composition not yet defined\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Identified histone H3 serine 10 as a conserved mitotic substrate balanced by the opposing phosphatase, generalizing the kinase-phosphatase axis to chromatin.\",\n      \"evidence\": \"Genetic analysis and phospho-H3 staining in S. cerevisiae and C. elegans\",\n      \"pmids\": [\"10975519\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of H3S10ph for segregation not resolved\", \"Direct vs indirect phosphorylation in vivo not separated here\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Defined the kinase as the agent of bi-orientation and tension-sensing, distinguishing tension defects from attachment defects in checkpoint signaling.\",\n      \"evidence\": \"Live imaging of kinetochore attachment turnover, checkpoint arrest assays, and in vitro kinase/microtubule-binding assays on Sli15 and Dam1\",\n      \"pmids\": [\"11731476\", \"11853667\", \"11724818\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not show how tension is read mechanically\", \"Relative contribution of individual substrates unquantified\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrated directly that the kinase generates the checkpoint signal by converting tensionless attachments into unattached kinetochores, and uncovered methylation antagonism as a substrate-level control.\",\n      \"evidence\": \"Analog-sensitive kinase allele with checkpoint and attachment assays; in vitro Set1 methylation inhibiting Dam1 phosphorylation\",\n      \"pmids\": [\"16327780\", \"16143104\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physical basis of detachment after phosphorylation not fully defined\", \"Generality of methyl-phospho switch to other substrates unknown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Resolved that the opposing phosphatase acts on the kinase's substrates rather than on the kinase itself, clarifying the directionality of the regulatory balance.\",\n      \"evidence\": \"Phosphorylation assays, localization, and dosage suppressor genetics on Glc7/PP1 regulatory subunits Gip3/Gip4 and Dam1\",\n      \"pmids\": [\"16537909\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Spatial coordination of phosphatase targeting incompletely mapped\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Extended kinase function to meiotic cohesion protection and centrosome-driven spindle assembly through new substrates and recruitment factors.\",\n      \"evidence\": \"Genetic/localization analysis of Sgo1-dependent recruitment and PP2A-Rts1 maintenance; phospho-site mutagenesis of the midzone protein Ase1\",\n      \"pmids\": [\"17371833\", \"17765685\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct phosphorylation of cohesion machinery not shown\", \"Ase1 role outside Cin8-deficient context unclear\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Built the mechanistic detail of substrate regulation by tension and added core CPC subunit Nbl1, while extending the kinase to mitotic chromatin RNA control and meiotic SC disassembly.\",\n      \"evidence\": \"Phospho-specific antibodies tracking Dam1/Ndc80 phosphorylation vs tension, Co-purification of Nbl1, RNAi/imaging of XIST retention, and meiotic SC disassembly genetics\",\n      \"pmids\": [\"19923271\", \"19158380\", \"19704020\", \"19822728\", \"19759266\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why single-substrate phospho-mutants are insufficient remains open\", \"Mechanism linking H3 phosphorylation to RNA retention not defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Established Cdk1 as a direct upstream regulator that times CPC spindle binding, integrating Aurora B into the mitotic kinase network.\",\n      \"evidence\": \"In vitro kinase assay, phospho-site mutagenesis, and localization of Cdk1-phosphorylated Sli15/Ipl1 controlling Bim1 association\",\n      \"pmids\": [\"21727193\", \"22521784\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Coordination with phosphatase counteraction at anaphase not fully resolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showed the kinase remodels kinetochores and orchestrates attachment release for meiosis, defining a meiosis-specific structural role.\",\n      \"evidence\": \"Live imaging with chemical-genetic kinase inhibition and quantitative mass spectrometry showing Ipl1-dependent Ndc80 shedding in meiosis I\",\n      \"pmids\": [\"23371552\", \"26157162\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Substrate driving Ndc80 shedding not pinpointed\", \"Sequential kinase handoff mechanism with Mps1 incompletely mapped\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Expanded the regulatory network upstream and laterally — VRK1 cross-inhibition, haspin-dependent centromere recruitment, and inter-Aurora kinase regulation in meiosis.\",\n      \"evidence\": \"Co-IP and reciprocal in vitro kinase inhibition (VRK1); haspin inhibitor/knockout localization in spermatocytes; double-knockout mouse oocyte genetics (AURKB/AURKC)\",\n      \"pmids\": [\"29340707\", \"35694956\", \"30415701\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Quantitative balance among recruitment inputs unresolved\", \"Tissue specificity of inter-kinase regulation not generalized\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined an interphase transcriptional function in which promoter H3S10ph activates growth genes, and positioned AURKB as a context-dependent therapeutic target.\",\n      \"evidence\": \"ChIP of H3S10ph at CCND1, EHMT phosphorylation in B-ALL, and inhibitor studies in NSCLC, TNBC, and KSHV cleavage models\",\n      \"pmids\": [\"31982864\", \"30733284\", \"31000705\", \"36627281\", \"30917319\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs recruited H3S10ph at specific promoters not always separated\", \"Generality of transcriptional roles beyond surveyed cancers unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified post-translational stabilization controlling AURKB abundance, linking deubiquitination to oncogenic signaling.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, ChIP, and Usp29 knockout mice defining a FUBP1-USP29-AURKB axis\",\n      \"pmids\": [\"38233848\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether stabilization affects mitotic vs transcriptional pools unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed kinase-independent and noncanonical activities, including RNA-binding-protein regulation and additional promoter H3S10ph targets.\",\n      \"evidence\": \"Co-IP/RNA-IP and mRNA stability assays for HNRNPM/PSAT1 (kinase-independent), DHX9 and MAD2L2 interaction studies, and ChIP at the CCNE1 promoter\",\n      \"pmids\": [\"40784984\", \"38713155\", \"38515112\", \"38874176\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of kinase-independent RNA-protein interference unknown\", \"DHX9 interaction rests on Co-IP without reciprocal validation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How AURKB partitions between its canonical CPC mitotic role and its emerging kinase-independent and interphase transcriptional functions, and how these are coordinately regulated in normal versus malignant cells, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model integrating mitotic and transcriptional pools\", \"Substrate hierarchy across contexts not quantified\", \"Structural determinants of kinase-independent functions undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [1, 8, 17, 27, 28, 31, 45]},\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [2, 15, 33, 44]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [2, 15, 33, 44, 42]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [33, 44, 42, 27]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [8, 17, 24, 20]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [46]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2, 8, 27]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [4, 8, 13, 25]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 5, 9, 20, 24]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [21, 36]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [2, 15]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 6, 7, 10, 16]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [13, 19, 23, 26, 32, 40]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [33, 44, 42, 27]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [2, 15, 11]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [30, 34, 35, 36, 41, 43, 46]}\n    ],\n    \"complexes\": [\"Chromosomal passenger complex (CPC)\"],\n    \"partners\": [\"INCENP\", \"BIRC5\", \"Borealin/Nbl1\", \"DAM1\", \"NDC80\", \"VRK1\", \"USP29\", \"MAD2L2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}