{"gene":"CENPN","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2009,"finding":"CENP-N selectively binds CENP-A nucleosomes but not H3 nucleosomes or soluble CENP-A-H4 tetramers in a DNA sequence-independent manner. Mutations reducing CENP-N affinity for CENP-A nucleosomes caused defects in CENP-N localization and dominant-negative effects on recruitment of CENP-H, CENP-I, and CENP-K to centromeres. siRNA depletion of CENP-N reduced assembly of nascent CENP-A into centromeric chromatin.","method":"In vitro nucleosome binding assays, mutagenesis, siRNA depletion, fluorescence microscopy","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — direct in vitro binding assay with mutagenesis, siRNA KD with specific centromere assembly phenotype; foundational paper replicated by multiple subsequent studies","pmids":["19543270"],"is_preprint":false},{"year":2017,"finding":"Cryo-EM and biochemical studies revealed that CENP-N decodes the CENP-A nucleosome through charge and space complementarity with the L1 loop unique to CENP-A, and engages a 15-bp segment of nucleosomal DNA. Stable centromere recruitment of CENP-N additionally requires a coincident interaction with a binding motif on nucleosome-bound CENP-C.","method":"Cryo-EM structure, biochemical binding assays, mutagenesis, cell biological localization assays","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure with mutagenesis and cell biological validation, independently corroborated by concurrent Science paper","pmids":["29280735"],"is_preprint":false},{"year":2017,"finding":"Cryo-EM and biophysical studies showed CENP-N confers binding specificity to the CENP-A nucleosome through interactions with the L1 loop of CENP-A stabilized by electrostatic interactions with nucleosomal DNA. Residue-swapping experiments involving the L1 loop confirmed coevolution of CENP-N and CENP-A.","method":"Cryo-EM, biophysical assays (SPR/ITC), mutagenesis, residue-swapping experiments in Xenopus and human","journal":"Science (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure with mutagenesis and cross-species residue-swap validation; independently corroborates eLife 2017 paper","pmids":["29269420"],"is_preprint":false},{"year":2015,"finding":"The CENP-A-specific RG loop (Arg80/Gly81) plays a dual regulatory role: it assists formation of a compact 'ladder-like' centromeric chromatin structure that conceals the loop and impairs CENP-N recruitment, and upon G1/S-phase transition centromeric chromatin switches to an open state exposing the RG loop to recruit CENP-N, establishing cell-cycle-dependent regulation of CENP-N centromere association.","method":"Biochemical chromatin compaction assays, mutational analysis of RG loop, cell cycle synchronization, fluorescence microscopy","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — mutagenesis combined with chromatin structural assays and cell cycle staging; single lab but multiple orthogonal methods","pmids":["25943375"],"is_preprint":false},{"year":2011,"finding":"FRET in living cells demonstrated that the N-terminus of CENP-N lies in close proximity to the N-terminus of CENP-A in vivo. CENP-N is bound to kinetochores during S phase and G2, largely absent during mitosis and G1, undergoes rapid exchange in G1 until mid-S phase when it becomes stably associated, and the majority loads during S phase and dissociates in G2, suggesting a role as a fidelity factor during centromeric replication.","method":"FRET in live cells, fluorescence recovery after photobleaching (FRAP), live-cell imaging with cell cycle markers","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — FRET provides direct in vivo proximity measurement, FRAP quantifies dynamics, multiple orthogonal approaches in single study","pmids":["22100916"],"is_preprint":false},{"year":2022,"finding":"CENP-N promotes stacking of CENP-A-containing mononucleosomes and nucleosomal arrays through an interaction between the α6 helix of CENP-N and the DNA of a neighboring nucleosome, driving densely packed higher-order chromatin structure at the centromere in cells.","method":"Cryo-EM structures of nucleosome stacks, biophysical characterization, mutagenesis of α6 helix, cell-based chromatin compaction assays","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cryo-EM structure with biophysical characterization and mutagenesis validated in cells; single lab but multiple orthogonal methods","pmids":["35422519"],"is_preprint":false},{"year":2023,"finding":"CDK1 phosphorylates CENP-N during mitosis (identified by mass spectrometry), and this phosphorylation modulates the CENP-L–CENP-N interaction for accurate chromosome segregation and CCAN organization. Perturbation of CENP-N phosphorylation prevents proper chromosome alignment and activates the spindle assembly checkpoint.","method":"Mass spectrometry identification of phosphorylation sites, phosphomutant cell biology, CDK1 kinase assays, chromosome alignment assays, spindle assembly checkpoint readout","journal":"Journal of molecular cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS-identified phosphorylation with phosphomutant functional validation; single lab, abstract does not detail full mutagenesis rescue controls","pmids":["37365681"],"is_preprint":false},{"year":2019,"finding":"In silkworm (Bombyx mori holocentric chromosomes), CENP-N localizes to kinetochores and RNAi against CENP-N disrupts kinetochore function. Affinity purification/mass spectrometry identified HSC70 as a CENP-N interacting protein; HSC70 stabilizes CENP-N by inhibiting ubiquitin-proteasome-mediated degradation, controlling cell-cycle-regulated turnover of CENP-N at centromeres.","method":"RNAi, cellular localization by immunofluorescence, affinity purification/mass spectrometry, co-immunoprecipitation, proteasome inhibition assays","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2-3 / Weak — Co-IP and functional RNAi in a non-mammalian (silkworm) system; single lab, ortholog relevance uncertain given absent CENP-A/C in this species","pmids":["31756960"],"is_preprint":false},{"year":2024,"finding":"CENP-N inhibits autophagy in nasopharyngeal carcinoma cells by preventing nuclear translocation of phospho-CREB, reducing p-CREB binding to the VAMP8 promoter and thereby suppressing VAMP8 transcription. Sequential knockdown experiments showed VAMP8 is epistatic to CENP-N in this pathway; knockdown of CENPN increases autophagy, enhances VAMP8 expression, and sensitizes NPC cells to paclitaxel.","method":"siRNA/shRNA knockdown, transcriptome sequencing, ChIP assay for p-CREB at VAMP8 promoter, Western blot, autophagy assays (LC3/TEM), xenograft mouse model","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP directly demonstrates CREB-VAMP8 promoter binding regulated by CENPN, epistasis via double knockdown, in vivo validation; single lab","pmids":["37776538"],"is_preprint":false},{"year":2025,"finding":"CENP-N directly binds STAT3 (confirmed by co-immunoprecipitation, GST pull-down, and protein truncation tests) and promotes STAT3 phosphorylation and nuclear translocation, which drives transcription of USP37. This CENPN/STAT3/USP37 axis promotes invasion and metastasis of nasopharyngeal carcinoma cells in vitro and in vivo.","method":"Co-immunoprecipitation, GST pull-down, protein truncation mapping, luciferase reporter assay, ChIP, transcriptome sequencing, xenograft mouse model","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and GST pull-down establish direct binding; luciferase and ChIP confirm transcriptional regulation; single lab","pmids":["40458725"],"is_preprint":false},{"year":2024,"finding":"CENP-N directly interacts with SEPT9 (septin 9) and enhances SEPT9 methylation at specific lysine residues, upregulating key glycolytic enzymes and promoting aerobic glycolysis, CRC cell proliferation, migration, and liver metastasis in vivo.","method":"Co-immunoprecipitation, methylation-specific PCR, ChIP assay, in vitro functional assays, in vivo xenograft with fluorescence imaging and histology","journal":"Clinical & experimental metastasis","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single Co-IP showing interaction; methylation mechanism not fully reconstituted; abstract does not specify how CENP-N mediates methyltransferase activity","pmids":["39424682"],"is_preprint":false},{"year":2024,"finding":"CENP-N interacts with MDM2 and promotes pancreatic adenocarcinoma progression by targeting the p53 signaling pathway, as shown by bioinformatic enrichment analysis and in vitro co-immunoprecipitation.","method":"Protein-protein interaction network analysis, Co-immunoprecipitation, CCK8, Transwell assays","journal":"Archives of medical science : AMS","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP for MDM2 interaction; p53 pathway placement relies largely on enrichment analysis; single lab","pmids":["39649279"],"is_preprint":false}],"current_model":"CENP-N is a constitutive centromere-associated network (CCAN) protein that selectively recognizes CENP-A nucleosomes by reading the CENP-A-specific L1/RG loop through charge and shape complementarity while simultaneously contacting nucleosomal DNA and nucleosome-bound CENP-C; its centromere association is cell-cycle regulated (enriched in S/G2, absent in mitosis/G1) through conformational transitions of centromeric chromatin, is dynamically controlled by CDK1-mediated phosphorylation that modulates CENP-L interaction, and CENP-N additionally compacts centromeric chromatin into higher-order stacked nucleosome arrays via its α6 helix, collectively enabling proper kinetochore assembly and accurate chromosome segregation."},"narrative":{"mechanistic_narrative":"CENP-N is a constitutive centromere component that establishes the molecular basis for selective recognition of CENP-A nucleosomes, thereby seeding kinetochore assembly and licensing accurate chromosome segregation [PMID:19543270]. It distinguishes CENP-A from canonical H3 chromatin by decoding the CENP-A-specific L1/RG loop through charge and shape complementarity while clamping an adjacent segment of nucleosomal DNA, and stable centromere recruitment additionally requires a coincident contact with nucleosome-bound CENP-C [PMID:29280735, PMID:29269420]. Through these contacts CENP-N is required for centromeric loading of nascent CENP-A and for downstream recruitment of CCAN members CENP-H, CENP-I, and CENP-K, with binding-deficient mutants acting dominant-negatively [PMID:19543270]. CENP-N centromere association is cell-cycle restricted—enriched and stably bound during S/G2 but largely absent in mitosis and G1—because the CENP-A RG loop is concealed within a compact chromatin state and becomes exposed only upon a G1/S conformational switch to an open configuration [PMID:25943375, PMID:22100916]. Beyond reading individual nucleosomes, CENP-N drives higher-order centromeric chromatin compaction by using its α6 helix to bridge the DNA of neighboring nucleosomes into stacked arrays [PMID:35422519], and its interaction with CENP-L is modulated by CDK1-mediated mitotic phosphorylation, which is required for proper chromosome alignment and CCAN organization [PMID:37365681]. A separate body of cancer-cell work places CENP-N in transcriptional and signaling circuits—suppressing autophagy via p-CREB/VAMP8 and promoting tumor invasion through a STAT3/USP37 axis [PMID:37776538, PMID:40458725]—but these activities are documented only in specific tumor contexts and their mechanistic relationship to its centromeric function is uncharacterized in the available corpus.","teleology":[{"year":2009,"claim":"Established that CENP-N is the centromere protein that selectively reads CENP-A nucleosomes and acts upstream of the CCAN, answering how the centromere distinguishes CENP-A chromatin from bulk H3 chromatin.","evidence":"In vitro nucleosome binding assays with mutagenesis plus siRNA depletion and fluorescence microscopy in human cells","pmids":["19543270"],"confidence":"High","gaps":["Structural basis of CENP-A discrimination not yet resolved","Direct contact residues on CENP-A undefined at this stage"]},{"year":2011,"claim":"Defined the cell-cycle dynamics of CENP-N at centromeres, showing it is a transient S/G2 factor rather than a constitutively bound subunit, and positioned it as a fidelity factor during centromeric replication.","evidence":"FRET and FRAP live-cell imaging with cell-cycle markers","pmids":["22100916"],"confidence":"High","gaps":["Molecular trigger for the timed loading/dissociation not identified here","Functional consequence of S-phase loading on segregation not directly tested"]},{"year":2015,"claim":"Explained the mechanism of cell-cycle-regulated recruitment by linking the CENP-A RG loop to a switchable compact-versus-open centromeric chromatin state that conceals or exposes the CENP-N binding determinant.","evidence":"Biochemical chromatin compaction assays, RG-loop mutagenesis, and cell-cycle synchronization with microscopy","pmids":["25943375"],"confidence":"High","gaps":["Factors driving the compaction switch not fully defined","Single-lab structural model of the ladder-like state"]},{"year":2017,"claim":"Resolved the structural code for CENP-A recognition: cryo-EM showed CENP-N decodes the CENP-A L1 loop via charge/shape complementarity stabilized by nucleosomal DNA, with CENP-C providing a coincident anchoring contact for stable recruitment.","evidence":"Two independent cryo-EM structures with biophysical binding assays, mutagenesis, and cross-species L1-loop residue-swapping (eLife and Science)","pmids":["29280735","29269420"],"confidence":"High","gaps":["How CENP-C and CENP-A contacts are temporally coordinated unclear","Higher-order chromatin role not addressed by mononucleosome structures"]},{"year":2022,"claim":"Extended CENP-N's role beyond single-nucleosome recognition by showing it physically compacts centromeric chromatin into stacked nucleosome arrays through its α6 helix.","evidence":"Cryo-EM of nucleosome stacks, biophysical characterization, α6-helix mutagenesis, and cell-based compaction assays","pmids":["35422519"],"confidence":"High","gaps":["How compaction is reconciled with the open-state requirement for recruitment unresolved","Functional consequence of stacking for kinetochore assembly not directly tested"]},{"year":2023,"claim":"Identified post-translational control of CENP-N, showing CDK1 phosphorylation modulates the CENP-L–CENP-N interaction to enable proper chromosome alignment and CCAN organization.","evidence":"Mass spectrometry phosphosite mapping, CDK1 kinase assays, phosphomutant cell biology, and spindle assembly checkpoint readouts","pmids":["37365681"],"confidence":"Medium","gaps":["Full mutagenesis rescue controls not detailed in abstract","Specific phosphosites and their structural effect on CENP-L binding not defined"]},{"year":2019,"claim":"Addressed CENP-N stability regulation, identifying HSC70 as a chaperone that protects CENP-N from ubiquitin-proteasome degradation to control its cell-cycle turnover at centromeres.","evidence":"RNAi, immunofluorescence localization, affinity purification/MS, Co-IP, and proteasome inhibition in silkworm (Bombyx mori)","pmids":["31756960"],"confidence":"Medium","gaps":["Relevance to mammalian CENP-N uncertain given holocentric, CENP-A/C-divergent system","Single lab, single Co-IP for HSC70 interaction"]},{"year":2024,"claim":"Implicated CENP-N in a non-centromeric transcriptional circuit, showing it suppresses autophagy by blocking p-CREB nuclear translocation and VAMP8 transcription in nasopharyngeal carcinoma.","evidence":"Knockdown, transcriptome sequencing, ChIP for p-CREB at the VAMP8 promoter, autophagy assays, and xenograft model","pmids":["37776538"],"confidence":"Medium","gaps":["Mechanistic link to CENP-N's centromeric function unclear","How CENP-N controls p-CREB localization not defined"]},{"year":2025,"claim":"Defined a CENP-N/STAT3/USP37 signaling axis, with direct CENP-N–STAT3 binding promoting STAT3 phosphorylation/nuclear translocation to drive tumor invasion and metastasis.","evidence":"Reciprocal Co-IP, GST pull-down, truncation mapping, luciferase reporter, ChIP, and xenograft model in NPC cells","pmids":["40458725"],"confidence":"Medium","gaps":["Single-lab study","How a centromeric protein engages cytoplasmic/nuclear STAT3 signaling mechanistically unresolved"]},{"year":2024,"claim":"Reported additional tumor-context partners (SEPT9, MDM2) linking CENP-N to glycolysis and p53 signaling.","evidence":"Co-IP, methylation-specific PCR, ChIP, bioinformatic enrichment, and in vitro/in vivo functional assays in CRC and pancreatic cancer","pmids":["39424682","39649279"],"confidence":"Low","gaps":["Single Co-IP interactions without reconstitution","Methyltransferase mechanism for SEPT9 unspecified; p53 link relies on enrichment analysis"]},{"year":null,"claim":"How CENP-N's well-defined centromeric/kinetochore activity mechanistically connects to the reported cytoplasmic and transcriptional cancer signaling roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking centromere function to STAT3/CREB/MDM2 signaling","Tumor-context partners not validated in normal cell physiology","Whether signaling roles require chromatin binding is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[1,2,5]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,3,4]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[1,2,5]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,4,6]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[3,5]}],"complexes":["CCAN","kinetochore"],"partners":["CENPA","CENPC","CENPL","STAT3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96H22","full_name":"Centromere protein N","aliases":["Interphase centromere complex protein 32"],"length_aa":339,"mass_kda":39.6,"function":"Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPN is the first protein to bind specifically to CENPA nucleosomes and the direct binding of CENPA nucleosomes by CENPN is required for centromere assembly. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate","subcellular_location":"Nucleus; Chromosome, centromere, kinetochore","url":"https://www.uniprot.org/uniprotkb/Q96H22/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/CENPN","classification":"Common Essential","n_dependent_lines":1199,"n_total_lines":1208,"dependency_fraction":0.9925496688741722},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CENPN","total_profiled":1310},"omim":[{"mim_id":"611511","title":"MLF1-INTERACTING PROTEIN; MLF1IP","url":"https://www.omim.org/entry/611511"},{"mim_id":"611510","title":"CENTROMERIC PROTEIN T; CENPT","url":"https://www.omim.org/entry/611510"},{"mim_id":"611509","title":"CENTROMERIC PROTEIN N; CENPN","url":"https://www.omim.org/entry/611509"},{"mim_id":"610152","title":"CENTROMERIC PROTEIN M; CENPM","url":"https://www.omim.org/entry/610152"},{"mim_id":"607435","title":"ERA G-PROTEIN-LIKE 1; ERAL1","url":"https://www.omim.org/entry/607435"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"bone marrow","ntpm":35.4}],"url":"https://www.proteinatlas.org/search/CENPN"},"hgnc":{"alias_symbol":["FLJ13607","FLJ22660","BM039"],"prev_symbol":["C16orf60"]},"alphafold":{"accession":"Q96H22","domains":[{"cath_id":"-","chopping":"4-77","consensus_level":"high","plddt":94.8309,"start":4,"end":77},{"cath_id":"3.60.90","chopping":"84-207","consensus_level":"high","plddt":91.1973,"start":84,"end":207},{"cath_id":"3.10.20.720","chopping":"243-338","consensus_level":"high","plddt":86.1869,"start":243,"end":338}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96H22","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96H22-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96H22-F1-predicted_aligned_error_v6.png","plddt_mean":85.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CENPN","jax_strain_url":"https://www.jax.org/strain/search?query=CENPN"},"sequence":{"accession":"Q96H22","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96H22.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96H22/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96H22"}},"corpus_meta":[{"pmid":"19543270","id":"PMC_19543270","title":"Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N.","date":"2009","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19543270","citation_count":244,"is_preprint":false},{"pmid":"29280735","id":"PMC_29280735","title":"Decoding the centromeric nucleosome through CENP-N.","date":"2017","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/29280735","citation_count":101,"is_preprint":false},{"pmid":"29269420","id":"PMC_29269420","title":"Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N.","date":"2017","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/29269420","citation_count":99,"is_preprint":false},{"pmid":"25943375","id":"PMC_25943375","title":"Structural transitions of centromeric chromatin regulate the cell cycle-dependent recruitment of CENP-N.","date":"2015","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/25943375","citation_count":65,"is_preprint":false},{"pmid":"22100916","id":"PMC_22100916","title":"Dynamics of CENP-N kinetochore binding during the cell cycle.","date":"2011","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/22100916","citation_count":54,"is_preprint":false},{"pmid":"35422519","id":"PMC_35422519","title":"CENP-N promotes the compaction of centromeric chromatin.","date":"2022","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/35422519","citation_count":45,"is_preprint":false},{"pmid":"37776538","id":"PMC_37776538","title":"CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis.","date":"2024","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/37776538","citation_count":24,"is_preprint":false},{"pmid":"34646306","id":"PMC_34646306","title":"CENPN Acts as a Novel Biomarker that Correlates With the Malignant Phenotypes of Glioma Cells.","date":"2021","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34646306","citation_count":16,"is_preprint":false},{"pmid":"40104708","id":"PMC_40104708","title":"Diagnostics and immunological function of CENPN in human tumors: from pan-cancer analysis to validation in breast cancer.","date":"2025","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/40104708","citation_count":16,"is_preprint":false},{"pmid":"37365681","id":"PMC_37365681","title":"Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis.","date":"2023","source":"Journal of molecular cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/37365681","citation_count":13,"is_preprint":false},{"pmid":"35809496","id":"PMC_35809496","title":"LncRNA FAM225A activates the cGAS-STING signaling pathway by combining FUS to promote CENP-N expression and regulates the progression of nasopharyngeal carcinoma.","date":"2022","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/35809496","citation_count":9,"is_preprint":false},{"pmid":"37697245","id":"PMC_37697245","title":"Clinical implications and immune features of CENPN in breast cancer.","date":"2023","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/37697245","citation_count":8,"is_preprint":false},{"pmid":"37127048","id":"PMC_37127048","title":"Knockdown of CENPN Inhibits Glucose Metabolism and Induces G1 Arrest in Esophageal Cancer Cells by Regulating PI3K/AKT Signaling Pathway.","date":"2023","source":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme","url":"https://pubmed.ncbi.nlm.nih.gov/37127048","citation_count":5,"is_preprint":false},{"pmid":"37940975","id":"PMC_37940975","title":"Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown.","date":"2023","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37940975","citation_count":5,"is_preprint":false},{"pmid":"31756960","id":"PMC_31756960","title":"Heat Shock Cognate 70 Functions as A Chaperone for the Stability of Kinetochore Protein CENP-N in Holocentric Insect Silkworms.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31756960","citation_count":5,"is_preprint":false},{"pmid":"39424682","id":"PMC_39424682","title":"Disrupting CENP-N mediated SEPT9 methylation as a strategy to inhibit aerobic glycolysis and liver metastasis in colorectal cancer.","date":"2024","source":"Clinical & experimental metastasis","url":"https://pubmed.ncbi.nlm.nih.gov/39424682","citation_count":3,"is_preprint":false},{"pmid":"39649279","id":"PMC_39649279","title":"CENPN contributes to pancreatic carcinoma progression through the MDM2-mediated p53 signaling pathway.","date":"2024","source":"Archives of medical science : AMS","url":"https://pubmed.ncbi.nlm.nih.gov/39649279","citation_count":2,"is_preprint":false},{"pmid":"40458725","id":"PMC_40458725","title":"The CENPN/STAT3/USP37 signaling axis promotes invasion, migration and metastasis in nasopharyngeal carcinoma.","date":"2025","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40458725","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11001,"output_tokens":3225,"usd":0.040689,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10680,"output_tokens":3628,"usd":0.07205,"stage2_stop_reason":"end_turn"},"total_usd":0.112739,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"CENP-N selectively binds CENP-A nucleosomes but not H3 nucleosomes or soluble CENP-A-H4 tetramers in a DNA sequence-independent manner. Mutations reducing CENP-N affinity for CENP-A nucleosomes caused defects in CENP-N localization and dominant-negative effects on recruitment of CENP-H, CENP-I, and CENP-K to centromeres. siRNA depletion of CENP-N reduced assembly of nascent CENP-A into centromeric chromatin.\",\n      \"method\": \"In vitro nucleosome binding assays, mutagenesis, siRNA depletion, fluorescence microscopy\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — direct in vitro binding assay with mutagenesis, siRNA KD with specific centromere assembly phenotype; foundational paper replicated by multiple subsequent studies\",\n      \"pmids\": [\"19543270\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Cryo-EM and biochemical studies revealed that CENP-N decodes the CENP-A nucleosome through charge and space complementarity with the L1 loop unique to CENP-A, and engages a 15-bp segment of nucleosomal DNA. Stable centromere recruitment of CENP-N additionally requires a coincident interaction with a binding motif on nucleosome-bound CENP-C.\",\n      \"method\": \"Cryo-EM structure, biochemical binding assays, mutagenesis, cell biological localization assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure with mutagenesis and cell biological validation, independently corroborated by concurrent Science paper\",\n      \"pmids\": [\"29280735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Cryo-EM and biophysical studies showed CENP-N confers binding specificity to the CENP-A nucleosome through interactions with the L1 loop of CENP-A stabilized by electrostatic interactions with nucleosomal DNA. Residue-swapping experiments involving the L1 loop confirmed coevolution of CENP-N and CENP-A.\",\n      \"method\": \"Cryo-EM, biophysical assays (SPR/ITC), mutagenesis, residue-swapping experiments in Xenopus and human\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure with mutagenesis and cross-species residue-swap validation; independently corroborates eLife 2017 paper\",\n      \"pmids\": [\"29269420\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The CENP-A-specific RG loop (Arg80/Gly81) plays a dual regulatory role: it assists formation of a compact 'ladder-like' centromeric chromatin structure that conceals the loop and impairs CENP-N recruitment, and upon G1/S-phase transition centromeric chromatin switches to an open state exposing the RG loop to recruit CENP-N, establishing cell-cycle-dependent regulation of CENP-N centromere association.\",\n      \"method\": \"Biochemical chromatin compaction assays, mutational analysis of RG loop, cell cycle synchronization, fluorescence microscopy\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — mutagenesis combined with chromatin structural assays and cell cycle staging; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"25943375\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"FRET in living cells demonstrated that the N-terminus of CENP-N lies in close proximity to the N-terminus of CENP-A in vivo. CENP-N is bound to kinetochores during S phase and G2, largely absent during mitosis and G1, undergoes rapid exchange in G1 until mid-S phase when it becomes stably associated, and the majority loads during S phase and dissociates in G2, suggesting a role as a fidelity factor during centromeric replication.\",\n      \"method\": \"FRET in live cells, fluorescence recovery after photobleaching (FRAP), live-cell imaging with cell cycle markers\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FRET provides direct in vivo proximity measurement, FRAP quantifies dynamics, multiple orthogonal approaches in single study\",\n      \"pmids\": [\"22100916\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CENP-N promotes stacking of CENP-A-containing mononucleosomes and nucleosomal arrays through an interaction between the α6 helix of CENP-N and the DNA of a neighboring nucleosome, driving densely packed higher-order chromatin structure at the centromere in cells.\",\n      \"method\": \"Cryo-EM structures of nucleosome stacks, biophysical characterization, mutagenesis of α6 helix, cell-based chromatin compaction assays\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM structure with biophysical characterization and mutagenesis validated in cells; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"35422519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CDK1 phosphorylates CENP-N during mitosis (identified by mass spectrometry), and this phosphorylation modulates the CENP-L–CENP-N interaction for accurate chromosome segregation and CCAN organization. Perturbation of CENP-N phosphorylation prevents proper chromosome alignment and activates the spindle assembly checkpoint.\",\n      \"method\": \"Mass spectrometry identification of phosphorylation sites, phosphomutant cell biology, CDK1 kinase assays, chromosome alignment assays, spindle assembly checkpoint readout\",\n      \"journal\": \"Journal of molecular cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS-identified phosphorylation with phosphomutant functional validation; single lab, abstract does not detail full mutagenesis rescue controls\",\n      \"pmids\": [\"37365681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In silkworm (Bombyx mori holocentric chromosomes), CENP-N localizes to kinetochores and RNAi against CENP-N disrupts kinetochore function. Affinity purification/mass spectrometry identified HSC70 as a CENP-N interacting protein; HSC70 stabilizes CENP-N by inhibiting ubiquitin-proteasome-mediated degradation, controlling cell-cycle-regulated turnover of CENP-N at centromeres.\",\n      \"method\": \"RNAi, cellular localization by immunofluorescence, affinity purification/mass spectrometry, co-immunoprecipitation, proteasome inhibition assays\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Weak — Co-IP and functional RNAi in a non-mammalian (silkworm) system; single lab, ortholog relevance uncertain given absent CENP-A/C in this species\",\n      \"pmids\": [\"31756960\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CENP-N inhibits autophagy in nasopharyngeal carcinoma cells by preventing nuclear translocation of phospho-CREB, reducing p-CREB binding to the VAMP8 promoter and thereby suppressing VAMP8 transcription. Sequential knockdown experiments showed VAMP8 is epistatic to CENP-N in this pathway; knockdown of CENPN increases autophagy, enhances VAMP8 expression, and sensitizes NPC cells to paclitaxel.\",\n      \"method\": \"siRNA/shRNA knockdown, transcriptome sequencing, ChIP assay for p-CREB at VAMP8 promoter, Western blot, autophagy assays (LC3/TEM), xenograft mouse model\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP directly demonstrates CREB-VAMP8 promoter binding regulated by CENPN, epistasis via double knockdown, in vivo validation; single lab\",\n      \"pmids\": [\"37776538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CENP-N directly binds STAT3 (confirmed by co-immunoprecipitation, GST pull-down, and protein truncation tests) and promotes STAT3 phosphorylation and nuclear translocation, which drives transcription of USP37. This CENPN/STAT3/USP37 axis promotes invasion and metastasis of nasopharyngeal carcinoma cells in vitro and in vivo.\",\n      \"method\": \"Co-immunoprecipitation, GST pull-down, protein truncation mapping, luciferase reporter assay, ChIP, transcriptome sequencing, xenograft mouse model\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and GST pull-down establish direct binding; luciferase and ChIP confirm transcriptional regulation; single lab\",\n      \"pmids\": [\"40458725\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CENP-N directly interacts with SEPT9 (septin 9) and enhances SEPT9 methylation at specific lysine residues, upregulating key glycolytic enzymes and promoting aerobic glycolysis, CRC cell proliferation, migration, and liver metastasis in vivo.\",\n      \"method\": \"Co-immunoprecipitation, methylation-specific PCR, ChIP assay, in vitro functional assays, in vivo xenograft with fluorescence imaging and histology\",\n      \"journal\": \"Clinical & experimental metastasis\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single Co-IP showing interaction; methylation mechanism not fully reconstituted; abstract does not specify how CENP-N mediates methyltransferase activity\",\n      \"pmids\": [\"39424682\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CENP-N interacts with MDM2 and promotes pancreatic adenocarcinoma progression by targeting the p53 signaling pathway, as shown by bioinformatic enrichment analysis and in vitro co-immunoprecipitation.\",\n      \"method\": \"Protein-protein interaction network analysis, Co-immunoprecipitation, CCK8, Transwell assays\",\n      \"journal\": \"Archives of medical science : AMS\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP for MDM2 interaction; p53 pathway placement relies largely on enrichment analysis; single lab\",\n      \"pmids\": [\"39649279\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CENP-N is a constitutive centromere-associated network (CCAN) protein that selectively recognizes CENP-A nucleosomes by reading the CENP-A-specific L1/RG loop through charge and shape complementarity while simultaneously contacting nucleosomal DNA and nucleosome-bound CENP-C; its centromere association is cell-cycle regulated (enriched in S/G2, absent in mitosis/G1) through conformational transitions of centromeric chromatin, is dynamically controlled by CDK1-mediated phosphorylation that modulates CENP-L interaction, and CENP-N additionally compacts centromeric chromatin into higher-order stacked nucleosome arrays via its α6 helix, collectively enabling proper kinetochore assembly and accurate chromosome segregation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CENP-N is a constitutive centromere component that establishes the molecular basis for selective recognition of CENP-A nucleosomes, thereby seeding kinetochore assembly and licensing accurate chromosome segregation [#0]. It distinguishes CENP-A from canonical H3 chromatin by decoding the CENP-A-specific L1/RG loop through charge and shape complementarity while clamping an adjacent segment of nucleosomal DNA, and stable centromere recruitment additionally requires a coincident contact with nucleosome-bound CENP-C [#1, #2]. Through these contacts CENP-N is required for centromeric loading of nascent CENP-A and for downstream recruitment of CCAN members CENP-H, CENP-I, and CENP-K, with binding-deficient mutants acting dominant-negatively [#0]. CENP-N centromere association is cell-cycle restricted—enriched and stably bound during S/G2 but largely absent in mitosis and G1—because the CENP-A RG loop is concealed within a compact chromatin state and becomes exposed only upon a G1/S conformational switch to an open configuration [#3, #4]. Beyond reading individual nucleosomes, CENP-N drives higher-order centromeric chromatin compaction by using its α6 helix to bridge the DNA of neighboring nucleosomes into stacked arrays [#5], and its interaction with CENP-L is modulated by CDK1-mediated mitotic phosphorylation, which is required for proper chromosome alignment and CCAN organization [#6]. A separate body of cancer-cell work places CENP-N in transcriptional and signaling circuits—suppressing autophagy via p-CREB/VAMP8 and promoting tumor invasion through a STAT3/USP37 axis [#8, #9]—but these activities are documented only in specific tumor contexts and their mechanistic relationship to its centromeric function is uncharacterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established that CENP-N is the centromere protein that selectively reads CENP-A nucleosomes and acts upstream of the CCAN, answering how the centromere distinguishes CENP-A chromatin from bulk H3 chromatin.\",\n      \"evidence\": \"In vitro nucleosome binding assays with mutagenesis plus siRNA depletion and fluorescence microscopy in human cells\",\n      \"pmids\": [\"19543270\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of CENP-A discrimination not yet resolved\", \"Direct contact residues on CENP-A undefined at this stage\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the cell-cycle dynamics of CENP-N at centromeres, showing it is a transient S/G2 factor rather than a constitutively bound subunit, and positioned it as a fidelity factor during centromeric replication.\",\n      \"evidence\": \"FRET and FRAP live-cell imaging with cell-cycle markers\",\n      \"pmids\": [\"22100916\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular trigger for the timed loading/dissociation not identified here\", \"Functional consequence of S-phase loading on segregation not directly tested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Explained the mechanism of cell-cycle-regulated recruitment by linking the CENP-A RG loop to a switchable compact-versus-open centromeric chromatin state that conceals or exposes the CENP-N binding determinant.\",\n      \"evidence\": \"Biochemical chromatin compaction assays, RG-loop mutagenesis, and cell-cycle synchronization with microscopy\",\n      \"pmids\": [\"25943375\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Factors driving the compaction switch not fully defined\", \"Single-lab structural model of the ladder-like state\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Resolved the structural code for CENP-A recognition: cryo-EM showed CENP-N decodes the CENP-A L1 loop via charge/shape complementarity stabilized by nucleosomal DNA, with CENP-C providing a coincident anchoring contact for stable recruitment.\",\n      \"evidence\": \"Two independent cryo-EM structures with biophysical binding assays, mutagenesis, and cross-species L1-loop residue-swapping (eLife and Science)\",\n      \"pmids\": [\"29280735\", \"29269420\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How CENP-C and CENP-A contacts are temporally coordinated unclear\", \"Higher-order chromatin role not addressed by mononucleosome structures\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended CENP-N's role beyond single-nucleosome recognition by showing it physically compacts centromeric chromatin into stacked nucleosome arrays through its α6 helix.\",\n      \"evidence\": \"Cryo-EM of nucleosome stacks, biophysical characterization, α6-helix mutagenesis, and cell-based compaction assays\",\n      \"pmids\": [\"35422519\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How compaction is reconciled with the open-state requirement for recruitment unresolved\", \"Functional consequence of stacking for kinetochore assembly not directly tested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified post-translational control of CENP-N, showing CDK1 phosphorylation modulates the CENP-L–CENP-N interaction to enable proper chromosome alignment and CCAN organization.\",\n      \"evidence\": \"Mass spectrometry phosphosite mapping, CDK1 kinase assays, phosphomutant cell biology, and spindle assembly checkpoint readouts\",\n      \"pmids\": [\"37365681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Full mutagenesis rescue controls not detailed in abstract\", \"Specific phosphosites and their structural effect on CENP-L binding not defined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Addressed CENP-N stability regulation, identifying HSC70 as a chaperone that protects CENP-N from ubiquitin-proteasome degradation to control its cell-cycle turnover at centromeres.\",\n      \"evidence\": \"RNAi, immunofluorescence localization, affinity purification/MS, Co-IP, and proteasome inhibition in silkworm (Bombyx mori)\",\n      \"pmids\": [\"31756960\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relevance to mammalian CENP-N uncertain given holocentric, CENP-A/C-divergent system\", \"Single lab, single Co-IP for HSC70 interaction\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Implicated CENP-N in a non-centromeric transcriptional circuit, showing it suppresses autophagy by blocking p-CREB nuclear translocation and VAMP8 transcription in nasopharyngeal carcinoma.\",\n      \"evidence\": \"Knockdown, transcriptome sequencing, ChIP for p-CREB at the VAMP8 promoter, autophagy assays, and xenograft model\",\n      \"pmids\": [\"37776538\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link to CENP-N's centromeric function unclear\", \"How CENP-N controls p-CREB localization not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined a CENP-N/STAT3/USP37 signaling axis, with direct CENP-N–STAT3 binding promoting STAT3 phosphorylation/nuclear translocation to drive tumor invasion and metastasis.\",\n      \"evidence\": \"Reciprocal Co-IP, GST pull-down, truncation mapping, luciferase reporter, ChIP, and xenograft model in NPC cells\",\n      \"pmids\": [\"40458725\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab study\", \"How a centromeric protein engages cytoplasmic/nuclear STAT3 signaling mechanistically unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Reported additional tumor-context partners (SEPT9, MDM2) linking CENP-N to glycolysis and p53 signaling.\",\n      \"evidence\": \"Co-IP, methylation-specific PCR, ChIP, bioinformatic enrichment, and in vitro/in vivo functional assays in CRC and pancreatic cancer\",\n      \"pmids\": [\"39424682\", \"39649279\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP interactions without reconstitution\", \"Methyltransferase mechanism for SEPT9 unspecified; p53 link relies on enrichment analysis\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CENP-N's well-defined centromeric/kinetochore activity mechanistically connects to the reported cytoplasmic and transcriptional cancer signaling roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking centromere function to STAT3/CREB/MDM2 signaling\", \"Tumor-context partners not validated in normal cell physiology\", \"Whether signaling roles require chromatin binding is untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [1, 2, 5]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [1, 2, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 4, 6]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [3, 5]}\n    ],\n    \"complexes\": [\"CCAN\", \"kinetochore\"],\n    \"partners\": [\"CENPA\", \"CENPC\", \"CENPL\", \"STAT3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}