{"gene":"DEPDC1","run_date":"2026-04-28T17:46:02","timeline":{"discoveries":[{"year":2007,"finding":"DEPDC1 protein localizes to the nucleus of bladder cancer cells, and siRNA-mediated suppression of DEPDC1 significantly inhibits growth of bladder cancer cells, establishing a role in tumor cell proliferation.","method":"Immunocytochemical staining for subcellular localization; siRNA knockdown with cell growth readout","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined cellular phenotype; single lab, two methods","pmids":["17452976"],"is_preprint":false},{"year":2010,"finding":"DEPDC1 physically interacts with the zinc finger transcription factor ZNF224 (a transcriptional repressor) in bladder cancer cells; this complex suppresses transcription of A20, an NF-κB inhibitor. Disrupting the DEPDC1-ZNF224 interaction with a cell-permeable peptide triggers A20 transcriptional activation and induces apoptosis in vitro and in vivo.","method":"Co-immunoprecipitation; immunocytochemistry colocalization; cell-permeable peptide inhibitor; in vitro and in vivo apoptosis assays","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP plus functional rescue in vitro and in vivo; moderate evidence with multiple orthogonal methods","pmids":["20587513"],"is_preprint":false},{"year":2014,"finding":"In C. elegans, the DEPDC1 ortholog LET-99 acts upstream of the heterotrimeric G-protein alpha subunit GPA-11 to control activation of the stress kinase JNK-1 in the anti-tubulin drug-induced apoptosis pathway. Human DEPDC1 similarly promotes vincristine-induced cell death via JNK-dependent degradation of the BCL-2 family protein MCL1.","method":"In vivo C. elegans RNAi screen; genetic epistasis; human cell-line JNK inhibition and MCL1 degradation assays","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1-2 — genetic epistasis in vivo combined with mechanistic validation in human cells; replicated across organisms","pmids":["25064737"],"is_preprint":false},{"year":2015,"finding":"DEPDC1 is highly expressed in mitotic phase cells; siRNA-mediated knockdown causes mitotic arrest, multipolar spindle structures, and multiple nuclei, accompanied by upregulation of A20 and cell cycle genes CCNB1 and CCNB2, establishing a pivotal role in mitotic progression.","method":"Synchronized cell expression analysis; immunofluorescence; siRNA knockdown with mitotic phenotype readout","journal":"BMB reports","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined mitotic phenotype; single lab, multiple orthogonal methods","pmids":["25902835"],"is_preprint":false},{"year":2017,"finding":"DEPDC1 isoform a localizes to the centrosome in metaphase (while isoform b localizes to the cell cortex during mitosis); phosphorylation of DEPDC1 at Ser110 is required for centrosomal localization of isoform a and for maintenance of centrosome integrity and bipolar spindle organization. Non-phosphorylatable mutants of DEPDC1a fail to rescue centrosome disruption caused by endogenous DEPDC1 depletion.","method":"Mass spectrometry identification of phospho-Ser110; biochemical phosphorylation assays; immunofluorescence localization; site-directed mutagenesis rescue experiments","journal":"Experimental cell research","confidence":"High","confidence_rationale":"Tier 1 — mass spectrometry plus mutagenesis plus functional rescue in a single study","pmids":["28602627"],"is_preprint":false},{"year":2017,"finding":"DEPDC1 interacts with the transcription factor E2F1 and increases its transcriptional activity, promoting G1-S phase cell cycle transition and tumor growth in prostate cancer cells.","method":"Co-immunoprecipitation; cell cycle analysis; in vivo xenograft model; E2F reporter assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP plus transcriptional reporter assay plus in vivo model; single lab","pmids":["28634077"],"is_preprint":false},{"year":2017,"finding":"DEPDC1 depletion in nasopharyngeal carcinoma cells causes upregulation of A20 and downregulation of multiple NF-κB downstream target genes (c-Myc, BCL2, CCND1, CCNB1, CCNB2, MMP2, MMP9, ICAM1, vimentin, Twist1), as well as mitotic defects including multipolar spindles and multiple nuclei, indicating DEPDC1 maintains NF-κB signaling and mitotic integrity.","method":"siRNA knockdown; immunofluorescence; RT-PCR and western blot of NF-κB targets; in vivo xenograft","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined pathway and cellular phenotype; single lab","pmids":["28969015"],"is_preprint":false},{"year":2019,"finding":"DEPDC1 knockdown in hepatocellular carcinoma significantly inhibits CCL20 and CCR6 expression; DEPDC1 promotes HCC cell proliferation, invasion, and angiogenesis through the CCL20/CCR6 signaling pathway, as shown by reversal of DEPDC1 overexpression effects upon CCL20 or CCR6 knockdown.","method":"DNA microarray; RT-qPCR; western blot; siRNA rescue experiments; in vitro angiogenesis assay","journal":"Oncology reports","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods including rescue experiments; single lab","pmids":["31322256"],"is_preprint":false},{"year":2019,"finding":"DEPDC1 promotes HCC cell viability and chemotherapy resistance through the JNK signaling pathway, as demonstrated by use of the JNK-specific inhibitor SP600125 reversing DEPDC1-mediated effects.","method":"JNK pharmacological inhibition; CCK8 cell viability; colony formation; in vivo xenograft","journal":"Bioscience reports","confidence":"Medium","confidence_rationale":"Tier 2 — pharmacological pathway inhibition with functional readout; single lab","pmids":["31189746"],"is_preprint":false},{"year":2020,"finding":"DEPDC1 upregulates RAS expression and thereby enhances ERK1/2 activity, inhibiting autophagy in lung adenocarcinoma cells. Knockdown or overexpression of DEPDC1 reciprocally modulates RAS-ERK1/2 signaling and autophagy markers.","method":"Western blot upon DEPDC1 knockdown and overexpression; RAS-ERK1/2 pathway analysis; autophagy marker analysis","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 3 — gain- and loss-of-function with pathway readout; single lab","pmids":["33021072"],"is_preprint":false},{"year":2021,"finding":"Linc-ROR acts as a competing endogenous RNA to stabilize DEPDC1 mRNA and regulates DEPDC1 mRNA stability by binding HNRNPK, thereby promoting HCC progression and angiogenesis through DEPDC1 upregulation.","method":"RNA-binding protein immunoprecipitation; miRNA sponge assay; DEPDC1 mRNA stability assays; functional proliferation and angiogenesis assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 — mechanistic RIP and ceRNA analyses; single lab","pmids":["34741030"],"is_preprint":false},{"year":2021,"finding":"DEPDC1 promotes HCC migration and invasion via Wnt/β-catenin signaling and epithelial-mesenchymal transition, with DEPDC1 expression modulating Wnt1, β-catenin, vimentin, and E-cadherin levels.","method":"Lentiviral DEPDC1 manipulation; western blot; in vivo bioluminescence imaging of metastasis; wound healing and transwell assays","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 — in vitro and in vivo validation; single lab","pmids":["34268303"],"is_preprint":false},{"year":2021,"finding":"ALPK2 kinase directly interacts with DEPDC1A and acts upstream of it; overexpression of DEPDC1A rescues the inhibitory effects of ALPK2 knockdown on bladder cancer cell proliferation, apoptosis, and migration, placing DEPDC1 downstream of ALPK2 in bladder cancer.","method":"Co-immunoprecipitation; siRNA knockdown; rescue overexpression experiments; in vivo xenograft","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP plus epistasis rescue; single lab","pmids":["34210956"],"is_preprint":false},{"year":2022,"finding":"FOXO3a binds to the DEPDC1 promoter and represses its transcription. DEPDC1 in turn promotes nephroblastoma cell proliferation, invasion, and migration via Wnt/β-catenin signaling (modulating p-GSK-3β, Wnt3a, and β-catenin), and DEPDC1 overexpression reverses FOXO3a-mediated inhibition.","method":"Dual-luciferase reporter assay; immunoprecipitation; siRNA/overexpression; western blot of Wnt/β-catenin components","journal":"Molecular medicine reports","confidence":"Medium","confidence_rationale":"Tier 2 — promoter-binding assay plus rescue experiments; single lab","pmids":["35795985"],"is_preprint":false},{"year":2022,"finding":"DEPDC1 physically interacts with FOXM1 in oral squamous cell carcinoma; this interaction facilitates Wnt/β-catenin signal transduction and promotes β-catenin nuclear localization.","method":"Co-immunoprecipitation; immunofluorescence colocalization; Wnt/β-catenin pathway reporter analysis","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 3 — Co-IP plus colocalization; single lab","pmids":["36072787"],"is_preprint":false},{"year":2022,"finding":"SIRT1 binds to the miR-20b-3p promoter to suppress miR-20b-3p expression; miR-20b-3p directly targets DEPDC1 to suppress its expression, and this SIRT1/miR-20b-3p/DEPDC1 axis mediates oxaliplatin resistance in colorectal cancer cells.","method":"Chromatin immunoprecipitation or promoter binding assay; luciferase reporter for miRNA-target validation; siRNA knockdown; cell viability and resistance assays","journal":"Cell biology international","confidence":"Medium","confidence_rationale":"Tier 2-3 — binding and targeting validated by reporter assay; single lab","pmids":["36200529"],"is_preprint":false},{"year":2023,"finding":"DEPDC1 interacts with KIF4A (confirmed by co-immunoprecipitation); DEPDC1 depletion activates the Hippo signaling pathway (increased p-LATS1 and p-YAP), and KIF4A upregulation reverses these effects and the associated suppression of osteosarcoma malignant behaviors.","method":"Co-immunoprecipitation; western blot of Hippo pathway components; siRNA and overexpression rescue experiments","journal":"Journal of orthopaedic surgery and research","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP plus pathway epistasis; single lab","pmids":["36849972"],"is_preprint":false},{"year":2023,"finding":"S100A16 directly binds DEPDC1 (confirmed by Co-IP); S100A16 promotes nephroblastoma progression and angiogenesis through PI3K/Akt/mTOR signaling, and DEPDC1 overexpression partially reverses the inhibitory effect of S100A16 knockdown.","method":"Co-immunoprecipitation; western blot of PI3K/Akt/mTOR components; siRNA and overexpression rescue; tube formation assay","journal":"Polish journal of pathology","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP plus rescue; single lab, weak evidence","pmids":["37955537"],"is_preprint":false},{"year":2024,"finding":"FOXM1 transcriptionally induces DEPDC1 expression by binding to its promoter; in turn, DEPDC1 physically interacts with FOXM1, promotes its nuclear translocation, and reinforces FOXM1 transcriptional activity, forming a positive feedback loop that drives hepatocarcinogenesis.","method":"Chromatin immunoprecipitation; Co-IP; nuclear fractionation; siRNA rescue; luciferase reporter","journal":"Cancer science","confidence":"High","confidence_rationale":"Tier 1-2 — ChIP plus reciprocal Co-IP plus nuclear translocation plus functional rescue; multiple orthogonal methods in single study","pmids":["39004911"],"is_preprint":false},{"year":2024,"finding":"DEPDC1 promotes glycolysis and malignant progression in renal cell carcinoma via the AKT/mTOR/HIF1α pathway; DEPDC1 knockdown reverses TKI resistance, as supported by RNA-seq and non-targeted metabolomics combined with protein-level pathway analysis.","method":"RNA-seq; non-targeted metabolomics; western blot of AKT/mTOR/HIF1α pathway; siRNA knockdown; TKI resistance assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 — multi-omics plus protein validation; single lab","pmids":["39068164"],"is_preprint":false},{"year":2024,"finding":"DEPDC1 interacts with TTK kinase (predicted by STRING and supported by binding assays) and upregulates RAS expression through TTK, enhancing ERK activity and thereby regulating autophagy-dependent glycolysis in osteosarcoma cells.","method":"Western blot; extracellular acidification rate; glucose uptake/lactate assays; siRNA knockdown; STRING-predicted interaction","journal":"Anti-cancer drugs","confidence":"Low","confidence_rationale":"Tier 3-4 — interaction based on STRING prediction with functional follow-up; no direct biochemical interaction confirmation reported","pmids":["39016842"],"is_preprint":false},{"year":2025,"finding":"METTL5-mediated m6A methylation of 18S rRNA enhances translation of DEPDC1 mRNA, promoting lung squamous cell carcinoma tumorigenesis; METTL5 knockdown markedly inhibits DEPDC1 protein levels and tumor cell proliferation and migration.","method":"m6A modification assays; METTL5 knockdown/overexpression; translation assays; in vitro and in vivo functional assays","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 — m6A modification with translational readout; single lab","pmids":["40018408"],"is_preprint":false},{"year":2025,"finding":"DUXAP8 lncRNA (induced by YY1) stabilizes DEPDC1 mRNA through HNRNPF binding and also acts as a miR-7-5p sponge to prevent miR-7-5p-mediated DEPDC1 suppression, thereby promoting HCC proliferation and metastasis.","method":"RNA immunoprecipitation; luciferase reporter assay; RIP for HNRNPF; miRNA sponge assay","journal":"Clinical and experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2-3 — multiple RNA-level mechanistic assays; single lab","pmids":["39992478"],"is_preprint":false},{"year":2025,"finding":"DEPDC1 interacts with KIF20A (confirmed by co-immunoprecipitation); DEPDC1 overexpression promotes liposarcoma cell proliferation, migration, and invasion through activation of the PI3K/AKT/mTOR signaling pathway, and KIF20A deletion partially mitigates these effects.","method":"Co-immunoprecipitation; western blot of PI3K/AKT/mTOR; siRNA/overexpression; in vitro proliferation/migration assays","journal":"Frontiers in endocrinology","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP plus pathway readout; single lab, weak evidence","pmids":["40600015"],"is_preprint":false}],"current_model":"DEPDC1 is a nuclear/centrosomal protein that is highly expressed in mitosis (with isoform a localizing to the centrosome in a Ser110 phosphorylation-dependent manner and isoform b to the cell cortex), regulates mitotic progression and centrosome integrity, promotes cancer cell proliferation by interacting with ZNF224 to repress the NF-κB inhibitor A20, interacts with E2F1 and FOXM1 to activate proliferative transcriptional programs, acts upstream of a LET-99/GPA-11/JNK pathway to mediate anti-tubulin drug-induced MCL1 degradation and apoptosis, and engages multiple oncogenic signaling axes (NF-κB, Wnt/β-catenin, RAS-ERK, JNK, AKT/mTOR/HIF1α, Hippo) in diverse cancer contexts."},"narrative":{"teleology":[{"year":2007,"claim":"Establishing that DEPDC1 is required for bladder cancer cell proliferation and localizes to the nucleus answered the basic question of whether this uncharacterized DEP-domain protein has oncogenic relevance.","evidence":"siRNA knockdown with growth inhibition readout; immunocytochemistry in bladder cancer cells","pmids":["17452976"],"confidence":"Medium","gaps":["No molecular mechanism or interacting partner identified","Single cancer type tested","No mitotic role yet recognized"]},{"year":2010,"claim":"Identification of ZNF224 as a DEPDC1 binding partner and A20 as a transcriptional target established the first mechanism: DEPDC1 co-represses A20 to sustain NF-κB signaling, and disrupting this interaction triggers apoptosis.","evidence":"Reciprocal Co-IP; cell-permeable peptide disruption; in vitro and in vivo apoptosis rescue","pmids":["20587513"],"confidence":"High","gaps":["How DEPDC1-ZNF224 is recruited to the A20 promoter is unknown","Whether this mechanism operates outside bladder cancer is untested"]},{"year":2014,"claim":"Cross-species genetic epistasis revealed that DEPDC1/LET-99 acts upstream of a heterotrimeric G-protein (GPA-11) to activate JNK, linking DEPDC1 to anti-tubulin drug-induced MCL1 degradation and apoptosis — the first non-transcriptional signaling axis for DEPDC1.","evidence":"C. elegans RNAi screen and epistasis; human cell JNK inhibition and MCL1 degradation assays","pmids":["25064737"],"confidence":"High","gaps":["Direct biochemical interaction between DEPDC1 and G-protein subunits not shown in human cells","Whether DEPDC1's DEP domain mediates G-protein coupling is unresolved"]},{"year":2015,"claim":"Demonstrating that DEPDC1 expression peaks in mitosis and that its knockdown causes multipolar spindles and multinucleation established DEPDC1 as a bona fide mitotic regulator, not merely a proliferation-associated gene.","evidence":"Synchronized cell expression profiling; immunofluorescence of mitotic defects upon siRNA depletion","pmids":["25902835"],"confidence":"Medium","gaps":["Mechanism by which DEPDC1 maintains spindle bipolarity unknown","No centrosomal localization yet determined"]},{"year":2017,"claim":"Mapping Ser110 phosphorylation as essential for centrosomal targeting of isoform a, and distinguishing cortical localization of isoform b, provided the first post-translational mechanism controlling DEPDC1 function and explained its role in centrosome integrity.","evidence":"Mass spectrometry; phospho-mutant rescue; immunofluorescence of isoform-specific localization","pmids":["28602627"],"confidence":"High","gaps":["Kinase responsible for Ser110 phosphorylation not identified","Centrosomal substrates or effectors of DEPDC1 unknown"]},{"year":2017,"claim":"Showing DEPDC1 interacts with E2F1 and enhances its transcriptional activity broadened DEPDC1's role from NF-κB co-repressor to a more general transcriptional co-activator promoting G1-S transition.","evidence":"Co-IP; E2F reporter assay; cell cycle analysis; xenograft in prostate cancer","pmids":["28634077"],"confidence":"Medium","gaps":["Whether DEPDC1 binds E2F1 directly or through a complex is unresolved","Genome-wide E2F1 target effects not mapped"]},{"year":2019,"claim":"DEPDC1 was connected to JNK-dependent chemoresistance in HCC and to CCL20/CCR6-mediated angiogenesis, revealing tissue-specific downstream effectors beyond NF-κB.","evidence":"JNK inhibitor reversal of DEPDC1 overexpression effects; CCL20/CCR6 siRNA rescue; in vitro angiogenesis","pmids":["31189746","31322256"],"confidence":"Medium","gaps":["Direct binding to JNK pathway components not demonstrated","Whether CCL20 regulation is transcriptional or post-transcriptional unclear"]},{"year":2021,"claim":"DEPDC1 was placed downstream of ALPK2 kinase and upstream of Wnt/β-catenin-driven EMT, and its mRNA was shown to be stabilized by lncRNA linc-ROR via HNRNPK, establishing both upstream regulators and a key oncogenic effector pathway.","evidence":"Co-IP and rescue epistasis for ALPK2; lentiviral manipulation with in vivo metastasis imaging for Wnt axis; RIP for HNRNPK-mediated mRNA stabilization","pmids":["34210956","34268303","34741030"],"confidence":"Medium","gaps":["Whether ALPK2 directly phosphorylates DEPDC1 is unknown","Mechanism by which DEPDC1 engages Wnt1/β-catenin not defined at protein level"]},{"year":2022,"claim":"Discovery of the DEPDC1-FOXM1 physical interaction and transcriptional repression of DEPDC1 by FOXO3a established transcription factor partnerships and a negative regulatory input, while also reinforcing Wnt/β-catenin as a shared downstream axis.","evidence":"Co-IP and colocalization for FOXM1; dual-luciferase promoter assay for FOXO3a; Wnt pathway reporter","pmids":["36072787","35795985"],"confidence":"Medium","gaps":["FOXM1-DEPDC1 stoichiometry and domain requirements undefined","FOXO3a regulation not confirmed outside nephroblastoma"]},{"year":2024,"claim":"A FOXM1-DEPDC1 positive feedback loop was demonstrated: FOXM1 transcriptionally induces DEPDC1 via promoter binding, while DEPDC1 reciprocally promotes FOXM1 nuclear translocation and activity, providing the first self-reinforcing circuit for DEPDC1 in hepatocarcinogenesis.","evidence":"ChIP; reciprocal Co-IP; nuclear fractionation; siRNA rescue; luciferase reporter","pmids":["39004911"],"confidence":"High","gaps":["Whether the feedback loop operates in non-hepatic cancers is unknown","Whether DEPDC1 directly chaperones FOXM1 or acts via an intermediary is unresolved"]},{"year":2024,"claim":"DEPDC1 was linked to metabolic reprogramming: it promotes glycolysis through AKT/mTOR/HIF1α and confers TKI resistance in renal cell carcinoma, expanding its role beyond proliferation to metabolic control.","evidence":"RNA-seq; non-targeted metabolomics; AKT/mTOR/HIF1α western blot; TKI resistance assays","pmids":["39068164"],"confidence":"Medium","gaps":["Direct interaction with AKT or mTOR not shown","Metabolic targets of HIF1α downstream of DEPDC1 not defined"]},{"year":2025,"claim":"Translational and post-transcriptional regulation of DEPDC1 was further defined: METTL5-mediated 18S rRNA m6A methylation enhances DEPDC1 mRNA translation, and the DUXAP8 lncRNA stabilizes DEPDC1 mRNA via HNRNPF and miR-7-5p sponging.","evidence":"m6A modification and translation assays for METTL5; RIP for HNRNPF; miRNA sponge luciferase reporter","pmids":["40018408","39992478"],"confidence":"Medium","gaps":["Whether METTL5-mediated regulation is DEPDC1-selective or part of global translational control unknown","Relative contribution of miRNA sponging versus HNRNPF-mediated stabilization not quantified"]},{"year":null,"claim":"Key mechanistic questions remain: the kinase phosphorylating Ser110, the structural basis of DEPDC1's DEP domain interactions, and whether DEPDC1 possesses intrinsic enzymatic activity or functions solely as a scaffold/co-regulator.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No crystal or cryo-EM structure available","DEP domain function not dissected biochemically","No unbiased proteomics of DEPDC1 interactome reported","Whether DEPDC1 has catalytic activity (e.g. GAP activity) is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,5,6,14,18]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,8,9,16]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,14,18]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,18]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[4]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3,4]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3,4,5]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,2,6,8,9,11,13,14,16,19]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,7,11,19]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,5,18]}],"complexes":[],"partners":["ZNF224","FOXM1","E2F1","KIF4A","ALPK2","KIF20A","S100A16"],"other_free_text":[]},"mechanistic_narrative":"DEPDC1 is a mitosis-associated nuclear and centrosomal protein that functions as a transcriptional co-regulator and signaling scaffold essential for cell proliferation, mitotic spindle integrity, and multiple oncogenic pathways. During mitosis, phosphorylation of DEPDC1 isoform a at Ser110 directs it to the centrosome, where it maintains centrosome integrity and bipolar spindle organization; its depletion causes multipolar spindles, mitotic arrest, and multinucleation [PMID:28602627, PMID:25902835]. DEPDC1 interacts with the zinc-finger repressor ZNF224 to silence the NF-κB inhibitor A20, thereby sustaining NF-κB signaling, and forms a positive-feedback loop with FOXM1 to promote FOXM1 nuclear translocation and transcriptional activity, while also engaging E2F1 to drive G1-S progression [PMID:20587513, PMID:39004911, PMID:28634077]. DEPDC1 additionally activates Wnt/β-catenin, JNK, RAS-ERK, and AKT/mTOR/HIF1α pathways across multiple tumor types, coupling proliferative signaling to drug resistance, glycolysis, and anti-tubulin drug-induced apoptosis via JNK-dependent MCL1 degradation [PMID:25064737, PMID:34268303, PMID:39068164]."},"prefetch_data":{"uniprot":{"accession":"Q5TB30","full_name":"DEP domain-containing protein 1A","aliases":[],"length_aa":811,"mass_kda":93.0,"function":"May be involved in transcriptional regulation as a transcriptional corepressor. The DEPDC1A-ZNF224 complex may play a critical role in bladder carcinogenesis by repressing the transcription of the A20 gene, leading to transport of NF-KB protein into the nucleus, resulting in suppression of apoptosis of bladder cancer cells","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q5TB30/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DEPDC1","classification":"Not Classified","n_dependent_lines":173,"n_total_lines":1208,"dependency_fraction":0.14321192052980133},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"FKBP5","stoichiometry":0.2},{"gene":"PTGES3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DEPDC1","total_profiled":1310},"omim":[{"mim_id":"612002","title":"DEP DOMAIN-CONTAINING PROTEIN 1; DEPDC1","url":"https://www.omim.org/entry/612002"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli fibrillar center","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"bone marrow","ntpm":4.7},{"tissue":"lymphoid tissue","ntpm":7.5},{"tissue":"testis","ntpm":7.5}],"url":"https://www.proteinatlas.org/search/DEPDC1"},"hgnc":{"alias_symbol":["DEP.8","FLJ20354","SDP35","DEPDC1A"],"prev_symbol":[]},"alphafold":{"accession":"Q5TB30","domains":[{"cath_id":"1.10.10.10","chopping":"13-106","consensus_level":"high","plddt":88.1331,"start":13,"end":106},{"cath_id":"1.10.555.10","chopping":"184-310_592-703","consensus_level":"medium","plddt":85.9687,"start":184,"end":703},{"cath_id":"-","chopping":"728-788","consensus_level":"high","plddt":81.1149,"start":728,"end":788}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5TB30","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5TB30-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5TB30-F1-predicted_aligned_error_v6.png","plddt_mean":60.22},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DEPDC1","jax_strain_url":"https://www.jax.org/strain/search?query=DEPDC1"},"sequence":{"accession":"Q5TB30","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5TB30.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5TB30/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5TB30"}},"corpus_meta":[{"pmid":"17452976","id":"PMC_17452976","title":"Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis.","date":"2007","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/17452976","citation_count":93,"is_preprint":false},{"pmid":"20587513","id":"PMC_20587513","title":"Cell-permeable peptide DEPDC1-ZNF224 interferes with transcriptional repression and oncogenicity in bladder cancer cells.","date":"2010","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/20587513","citation_count":86,"is_preprint":false},{"pmid":"27984115","id":"PMC_27984115","title":"Epigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1.","date":"2016","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/27984115","citation_count":58,"is_preprint":false},{"pmid":"30419349","id":"PMC_30419349","title":"DEPDC1, negatively regulated by miR-26b, facilitates cell proliferation via the up-regulation of FOXM1 expression in TNBC.","date":"2018","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/30419349","citation_count":51,"is_preprint":false},{"pmid":"25902835","id":"PMC_25902835","title":"DEPDC1 is a novel cell cycle related gene that regulates mitotic progression.","date":"2015","source":"BMB reports","url":"https://pubmed.ncbi.nlm.nih.gov/25902835","citation_count":45,"is_preprint":false},{"pmid":"28634077","id":"PMC_28634077","title":"DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer.","date":"2017","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/28634077","citation_count":44,"is_preprint":false},{"pmid":"25064737","id":"PMC_25064737","title":"DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis.","date":"2014","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/25064737","citation_count":41,"is_preprint":false},{"pmid":"28969015","id":"PMC_28969015","title":"DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/28969015","citation_count":37,"is_preprint":false},{"pmid":"31322256","id":"PMC_31322256","title":"DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway.","date":"2019","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/31322256","citation_count":31,"is_preprint":false},{"pmid":"34268303","id":"PMC_34268303","title":"Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/β-Catenin Signaling Pathway.","date":"2021","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/34268303","citation_count":27,"is_preprint":false},{"pmid":"36768316","id":"PMC_36768316","title":"Glycolysis-Related Gene Analyses Indicate That DEPDC1 Promotes the Malignant Progression of Oral Squamous Cell Carcinoma via the WNT/β-Catenin Signaling Pathway.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36768316","citation_count":25,"is_preprint":false},{"pmid":"34741030","id":"PMC_34741030","title":"Linc-ROR facilitates progression and angiogenesis of hepatocellular carcinoma by modulating DEPDC1 expression.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/34741030","citation_count":22,"is_preprint":false},{"pmid":"31189746","id":"PMC_31189746","title":"DEPDC1 promotes cell proliferation and suppresses sensitivity to chemotherapy in human hepatocellular carcinoma.","date":"2019","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/31189746","citation_count":20,"is_preprint":false},{"pmid":"39068164","id":"PMC_39068164","title":"DEPDC1 as a metabolic target regulates glycolysis in renal cell carcinoma through AKT/mTOR/HIF1α pathway.","date":"2024","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/39068164","citation_count":19,"is_preprint":false},{"pmid":"28555424","id":"PMC_28555424","title":"Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells.","date":"2017","source":"Journal of neuro-oncology","url":"https://pubmed.ncbi.nlm.nih.gov/28555424","citation_count":19,"is_preprint":false},{"pmid":"33021072","id":"PMC_33021072","title":"DEPDC1 up-regulates RAS expression to inhibit autophagy in lung adenocarcinoma cells.","date":"2020","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33021072","citation_count":18,"is_preprint":false},{"pmid":"36200529","id":"PMC_36200529","title":"SIRT1 enhances oxaliplatin resistance in colorectal cancer through microRNA-20b-3p/DEPDC1 axis.","date":"2022","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/36200529","citation_count":15,"is_preprint":false},{"pmid":"32642287","id":"PMC_32642287","title":"NNK-mediated upregulation of DEPDC1 stimulates the progression of oral squamous cell carcinoma by inhibiting CYP27B1 expression.","date":"2020","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/32642287","citation_count":15,"is_preprint":false},{"pmid":"28602627","id":"PMC_28602627","title":"Phosphorylation of DEPDC1 at Ser110 is required to maintain centrosome organization during mitosis.","date":"2017","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/28602627","citation_count":14,"is_preprint":false},{"pmid":"35466755","id":"PMC_35466755","title":"Long non-coding RNA DEPDC1-AS1 promotes proliferation and migration of human gastric cancer cells HGC-27 via the human antigen R-F11R pathway.","date":"2022","source":"The Journal of international medical research","url":"https://pubmed.ncbi.nlm.nih.gov/35466755","citation_count":13,"is_preprint":false},{"pmid":"38960258","id":"PMC_38960258","title":"Exosomal miR-130b-3p suppresses metastasis of non-small cell lung cancer cells by targeting DEPDC1 via TGF-β signaling pathway.","date":"2024","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/38960258","citation_count":12,"is_preprint":false},{"pmid":"28919988","id":"PMC_28919988","title":"Identification of a HLA-A*0201-restricted immunogenic epitope from the universal tumor antigen DEPDC1.","date":"2017","source":"Oncoimmunology","url":"https://pubmed.ncbi.nlm.nih.gov/28919988","citation_count":12,"is_preprint":false},{"pmid":"34210956","id":"PMC_34210956","title":"ALPK2 acts as tumor promotor in development of bladder cancer through targeting DEPDC1A.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/34210956","citation_count":12,"is_preprint":false},{"pmid":"36479633","id":"PMC_36479633","title":"DEPDC1 as a crucial factor in the progression of human osteosarcoma.","date":"2022","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36479633","citation_count":12,"is_preprint":false},{"pmid":"35582195","id":"PMC_35582195","title":"miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1.","date":"2022","source":"Open medicine (Warsaw, Poland)","url":"https://pubmed.ncbi.nlm.nih.gov/35582195","citation_count":11,"is_preprint":false},{"pmid":"36309731","id":"PMC_36309731","title":"Silencing eL31 suppresses the progression of colorectal cancer via targeting DEPDC1.","date":"2022","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36309731","citation_count":11,"is_preprint":false},{"pmid":"36849972","id":"PMC_36849972","title":"DEPDC1 and KIF4A synergistically inhibit the malignant biological behavior of osteosarcoma cells through Hippo signaling pathway.","date":"2023","source":"Journal of orthopaedic surgery and research","url":"https://pubmed.ncbi.nlm.nih.gov/36849972","citation_count":10,"is_preprint":false},{"pmid":"35795985","id":"PMC_35795985","title":"FOXO3a‑modulated DEPDC1 promotes malignant progression of nephroblastoma via the Wnt/β‑catenin signaling pathway.","date":"2022","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/35795985","citation_count":9,"is_preprint":false},{"pmid":"36072787","id":"PMC_36072787","title":"FOXM1 is regulated by DEPDC1 to facilitate development and metastasis of oral squamous cell carcinoma.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36072787","citation_count":7,"is_preprint":false},{"pmid":"39004911","id":"PMC_39004911","title":"FOXM1/DEPDC1 feedback loop promotes hepatocarcinogenesis and represents promising targets for cancer therapy.","date":"2024","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/39004911","citation_count":6,"is_preprint":false},{"pmid":"37955537","id":"PMC_37955537","title":"S100A16 cooperates with DEPDC1 to promote the progression and angiogenesis of nephroblastoma through PI3K/Akt/mTOR pathway.","date":"2023","source":"Polish journal of pathology : official journal of the Polish Society of Pathologists","url":"https://pubmed.ncbi.nlm.nih.gov/37955537","citation_count":6,"is_preprint":false},{"pmid":"34134185","id":"PMC_34134185","title":"[DEPDC1 is Highly Expressed in Lung Adenocarcinoma and Promotes Tumor Cell Proliferation].","date":"2021","source":"Zhongguo fei ai za zhi = Chinese journal of lung cancer","url":"https://pubmed.ncbi.nlm.nih.gov/34134185","citation_count":5,"is_preprint":false},{"pmid":"38564630","id":"PMC_38564630","title":"Comprehensive analysis and validation reveal DEPDC1 as a potential diagnostic biomarker associated with tumor immunity in non-small-cell lung cancer.","date":"2024","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/38564630","citation_count":3,"is_preprint":false},{"pmid":"39296974","id":"PMC_39296974","title":"Roles of DEPDC1 in various types of cancer (Review).","date":"2024","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/39296974","citation_count":2,"is_preprint":false},{"pmid":"39992478","id":"PMC_39992478","title":"YY1-mediated DUXAP8 facilitates HCC progression via modulating DEPDC1 expression.","date":"2025","source":"Clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39992478","citation_count":2,"is_preprint":false},{"pmid":"40018408","id":"PMC_40018408","title":"The human 18S rRNA m6A methyltransferase METTL5 promotes tumorigenesis via DEPDC1 in lung squamous cell carcinoma.","date":"2025","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40018408","citation_count":2,"is_preprint":false},{"pmid":"39016842","id":"PMC_39016842","title":"DEPDC1 affects autophagy-dependent glycolysis levels in human osteosarcoma cells by modulating RAS/ERK signaling through TTK.","date":"2024","source":"Anti-cancer drugs","url":"https://pubmed.ncbi.nlm.nih.gov/39016842","citation_count":2,"is_preprint":false},{"pmid":"40600015","id":"PMC_40600015","title":"DEPDC1 facilitated malignant phenotypes and disease progression of liposarcoma by modulating KIF20A.","date":"2025","source":"Frontiers in endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/40600015","citation_count":0,"is_preprint":false},{"pmid":"41851532","id":"PMC_41851532","title":"TCF7L2/DEPDC1 axis contributes to tumor progression by promoting cell proliferation, aerobic glycolysis, and immunosuppression in pancreatic cancer.","date":"2026","source":"Clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41851532","citation_count":0,"is_preprint":false},{"pmid":"41003831","id":"PMC_41003831","title":"LncRNA DEPDC1-AS1 drives the progression of endometrial carcinoma by regulating miR-508-3p.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41003831","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.25.655961","title":"Role of DEPDC1 in Glioblastoma Malignant Phenotype and Radiosensitivity","date":"2025-05-28","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.25.655961","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.23.604718","title":"Cell cycle-driven transcriptome maturation confers multilineage competence to cardiopharyngeal progenitors","date":"2024-07-23","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.23.604718","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":21603,"output_tokens":5247,"usd":0.071757},"stage2":{"model":"claude-opus-4-6","input_tokens":8878,"output_tokens":3280,"usd":0.189585},"total_usd":0.261342,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"DEPDC1 protein localizes to the nucleus of bladder cancer cells, and siRNA-mediated suppression of DEPDC1 significantly inhibits growth of bladder cancer cells, establishing a role in tumor cell proliferation.\",\n      \"method\": \"Immunocytochemical staining for subcellular localization; siRNA knockdown with cell growth readout\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotype; single lab, two methods\",\n      \"pmids\": [\"17452976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"DEPDC1 physically interacts with the zinc finger transcription factor ZNF224 (a transcriptional repressor) in bladder cancer cells; this complex suppresses transcription of A20, an NF-κB inhibitor. Disrupting the DEPDC1-ZNF224 interaction with a cell-permeable peptide triggers A20 transcriptional activation and induces apoptosis in vitro and in vivo.\",\n      \"method\": \"Co-immunoprecipitation; immunocytochemistry colocalization; cell-permeable peptide inhibitor; in vitro and in vivo apoptosis assays\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus functional rescue in vitro and in vivo; moderate evidence with multiple orthogonal methods\",\n      \"pmids\": [\"20587513\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In C. elegans, the DEPDC1 ortholog LET-99 acts upstream of the heterotrimeric G-protein alpha subunit GPA-11 to control activation of the stress kinase JNK-1 in the anti-tubulin drug-induced apoptosis pathway. Human DEPDC1 similarly promotes vincristine-induced cell death via JNK-dependent degradation of the BCL-2 family protein MCL1.\",\n      \"method\": \"In vivo C. elegans RNAi screen; genetic epistasis; human cell-line JNK inhibition and MCL1 degradation assays\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — genetic epistasis in vivo combined with mechanistic validation in human cells; replicated across organisms\",\n      \"pmids\": [\"25064737\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DEPDC1 is highly expressed in mitotic phase cells; siRNA-mediated knockdown causes mitotic arrest, multipolar spindle structures, and multiple nuclei, accompanied by upregulation of A20 and cell cycle genes CCNB1 and CCNB2, establishing a pivotal role in mitotic progression.\",\n      \"method\": \"Synchronized cell expression analysis; immunofluorescence; siRNA knockdown with mitotic phenotype readout\",\n      \"journal\": \"BMB reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined mitotic phenotype; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"25902835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"DEPDC1 isoform a localizes to the centrosome in metaphase (while isoform b localizes to the cell cortex during mitosis); phosphorylation of DEPDC1 at Ser110 is required for centrosomal localization of isoform a and for maintenance of centrosome integrity and bipolar spindle organization. Non-phosphorylatable mutants of DEPDC1a fail to rescue centrosome disruption caused by endogenous DEPDC1 depletion.\",\n      \"method\": \"Mass spectrometry identification of phospho-Ser110; biochemical phosphorylation assays; immunofluorescence localization; site-directed mutagenesis rescue experiments\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — mass spectrometry plus mutagenesis plus functional rescue in a single study\",\n      \"pmids\": [\"28602627\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"DEPDC1 interacts with the transcription factor E2F1 and increases its transcriptional activity, promoting G1-S phase cell cycle transition and tumor growth in prostate cancer cells.\",\n      \"method\": \"Co-immunoprecipitation; cell cycle analysis; in vivo xenograft model; E2F reporter assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP plus transcriptional reporter assay plus in vivo model; single lab\",\n      \"pmids\": [\"28634077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"DEPDC1 depletion in nasopharyngeal carcinoma cells causes upregulation of A20 and downregulation of multiple NF-κB downstream target genes (c-Myc, BCL2, CCND1, CCNB1, CCNB2, MMP2, MMP9, ICAM1, vimentin, Twist1), as well as mitotic defects including multipolar spindles and multiple nuclei, indicating DEPDC1 maintains NF-κB signaling and mitotic integrity.\",\n      \"method\": \"siRNA knockdown; immunofluorescence; RT-PCR and western blot of NF-κB targets; in vivo xenograft\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined pathway and cellular phenotype; single lab\",\n      \"pmids\": [\"28969015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"DEPDC1 knockdown in hepatocellular carcinoma significantly inhibits CCL20 and CCR6 expression; DEPDC1 promotes HCC cell proliferation, invasion, and angiogenesis through the CCL20/CCR6 signaling pathway, as shown by reversal of DEPDC1 overexpression effects upon CCL20 or CCR6 knockdown.\",\n      \"method\": \"DNA microarray; RT-qPCR; western blot; siRNA rescue experiments; in vitro angiogenesis assay\",\n      \"journal\": \"Oncology reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods including rescue experiments; single lab\",\n      \"pmids\": [\"31322256\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"DEPDC1 promotes HCC cell viability and chemotherapy resistance through the JNK signaling pathway, as demonstrated by use of the JNK-specific inhibitor SP600125 reversing DEPDC1-mediated effects.\",\n      \"method\": \"JNK pharmacological inhibition; CCK8 cell viability; colony formation; in vivo xenograft\",\n      \"journal\": \"Bioscience reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — pharmacological pathway inhibition with functional readout; single lab\",\n      \"pmids\": [\"31189746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DEPDC1 upregulates RAS expression and thereby enhances ERK1/2 activity, inhibiting autophagy in lung adenocarcinoma cells. Knockdown or overexpression of DEPDC1 reciprocally modulates RAS-ERK1/2 signaling and autophagy markers.\",\n      \"method\": \"Western blot upon DEPDC1 knockdown and overexpression; RAS-ERK1/2 pathway analysis; autophagy marker analysis\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — gain- and loss-of-function with pathway readout; single lab\",\n      \"pmids\": [\"33021072\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Linc-ROR acts as a competing endogenous RNA to stabilize DEPDC1 mRNA and regulates DEPDC1 mRNA stability by binding HNRNPK, thereby promoting HCC progression and angiogenesis through DEPDC1 upregulation.\",\n      \"method\": \"RNA-binding protein immunoprecipitation; miRNA sponge assay; DEPDC1 mRNA stability assays; functional proliferation and angiogenesis assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — mechanistic RIP and ceRNA analyses; single lab\",\n      \"pmids\": [\"34741030\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DEPDC1 promotes HCC migration and invasion via Wnt/β-catenin signaling and epithelial-mesenchymal transition, with DEPDC1 expression modulating Wnt1, β-catenin, vimentin, and E-cadherin levels.\",\n      \"method\": \"Lentiviral DEPDC1 manipulation; western blot; in vivo bioluminescence imaging of metastasis; wound healing and transwell assays\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vitro and in vivo validation; single lab\",\n      \"pmids\": [\"34268303\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"ALPK2 kinase directly interacts with DEPDC1A and acts upstream of it; overexpression of DEPDC1A rescues the inhibitory effects of ALPK2 knockdown on bladder cancer cell proliferation, apoptosis, and migration, placing DEPDC1 downstream of ALPK2 in bladder cancer.\",\n      \"method\": \"Co-immunoprecipitation; siRNA knockdown; rescue overexpression experiments; in vivo xenograft\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP plus epistasis rescue; single lab\",\n      \"pmids\": [\"34210956\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"FOXO3a binds to the DEPDC1 promoter and represses its transcription. DEPDC1 in turn promotes nephroblastoma cell proliferation, invasion, and migration via Wnt/β-catenin signaling (modulating p-GSK-3β, Wnt3a, and β-catenin), and DEPDC1 overexpression reverses FOXO3a-mediated inhibition.\",\n      \"method\": \"Dual-luciferase reporter assay; immunoprecipitation; siRNA/overexpression; western blot of Wnt/β-catenin components\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — promoter-binding assay plus rescue experiments; single lab\",\n      \"pmids\": [\"35795985\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DEPDC1 physically interacts with FOXM1 in oral squamous cell carcinoma; this interaction facilitates Wnt/β-catenin signal transduction and promotes β-catenin nuclear localization.\",\n      \"method\": \"Co-immunoprecipitation; immunofluorescence colocalization; Wnt/β-catenin pathway reporter analysis\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — Co-IP plus colocalization; single lab\",\n      \"pmids\": [\"36072787\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SIRT1 binds to the miR-20b-3p promoter to suppress miR-20b-3p expression; miR-20b-3p directly targets DEPDC1 to suppress its expression, and this SIRT1/miR-20b-3p/DEPDC1 axis mediates oxaliplatin resistance in colorectal cancer cells.\",\n      \"method\": \"Chromatin immunoprecipitation or promoter binding assay; luciferase reporter for miRNA-target validation; siRNA knockdown; cell viability and resistance assays\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — binding and targeting validated by reporter assay; single lab\",\n      \"pmids\": [\"36200529\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1 interacts with KIF4A (confirmed by co-immunoprecipitation); DEPDC1 depletion activates the Hippo signaling pathway (increased p-LATS1 and p-YAP), and KIF4A upregulation reverses these effects and the associated suppression of osteosarcoma malignant behaviors.\",\n      \"method\": \"Co-immunoprecipitation; western blot of Hippo pathway components; siRNA and overexpression rescue experiments\",\n      \"journal\": \"Journal of orthopaedic surgery and research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP plus pathway epistasis; single lab\",\n      \"pmids\": [\"36849972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"S100A16 directly binds DEPDC1 (confirmed by Co-IP); S100A16 promotes nephroblastoma progression and angiogenesis through PI3K/Akt/mTOR signaling, and DEPDC1 overexpression partially reverses the inhibitory effect of S100A16 knockdown.\",\n      \"method\": \"Co-immunoprecipitation; western blot of PI3K/Akt/mTOR components; siRNA and overexpression rescue; tube formation assay\",\n      \"journal\": \"Polish journal of pathology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP plus rescue; single lab, weak evidence\",\n      \"pmids\": [\"37955537\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"FOXM1 transcriptionally induces DEPDC1 expression by binding to its promoter; in turn, DEPDC1 physically interacts with FOXM1, promotes its nuclear translocation, and reinforces FOXM1 transcriptional activity, forming a positive feedback loop that drives hepatocarcinogenesis.\",\n      \"method\": \"Chromatin immunoprecipitation; Co-IP; nuclear fractionation; siRNA rescue; luciferase reporter\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — ChIP plus reciprocal Co-IP plus nuclear translocation plus functional rescue; multiple orthogonal methods in single study\",\n      \"pmids\": [\"39004911\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DEPDC1 promotes glycolysis and malignant progression in renal cell carcinoma via the AKT/mTOR/HIF1α pathway; DEPDC1 knockdown reverses TKI resistance, as supported by RNA-seq and non-targeted metabolomics combined with protein-level pathway analysis.\",\n      \"method\": \"RNA-seq; non-targeted metabolomics; western blot of AKT/mTOR/HIF1α pathway; siRNA knockdown; TKI resistance assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multi-omics plus protein validation; single lab\",\n      \"pmids\": [\"39068164\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DEPDC1 interacts with TTK kinase (predicted by STRING and supported by binding assays) and upregulates RAS expression through TTK, enhancing ERK activity and thereby regulating autophagy-dependent glycolysis in osteosarcoma cells.\",\n      \"method\": \"Western blot; extracellular acidification rate; glucose uptake/lactate assays; siRNA knockdown; STRING-predicted interaction\",\n      \"journal\": \"Anti-cancer drugs\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3-4 — interaction based on STRING prediction with functional follow-up; no direct biochemical interaction confirmation reported\",\n      \"pmids\": [\"39016842\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"METTL5-mediated m6A methylation of 18S rRNA enhances translation of DEPDC1 mRNA, promoting lung squamous cell carcinoma tumorigenesis; METTL5 knockdown markedly inhibits DEPDC1 protein levels and tumor cell proliferation and migration.\",\n      \"method\": \"m6A modification assays; METTL5 knockdown/overexpression; translation assays; in vitro and in vivo functional assays\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — m6A modification with translational readout; single lab\",\n      \"pmids\": [\"40018408\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DUXAP8 lncRNA (induced by YY1) stabilizes DEPDC1 mRNA through HNRNPF binding and also acts as a miR-7-5p sponge to prevent miR-7-5p-mediated DEPDC1 suppression, thereby promoting HCC proliferation and metastasis.\",\n      \"method\": \"RNA immunoprecipitation; luciferase reporter assay; RIP for HNRNPF; miRNA sponge assay\",\n      \"journal\": \"Clinical and experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — multiple RNA-level mechanistic assays; single lab\",\n      \"pmids\": [\"39992478\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DEPDC1 interacts with KIF20A (confirmed by co-immunoprecipitation); DEPDC1 overexpression promotes liposarcoma cell proliferation, migration, and invasion through activation of the PI3K/AKT/mTOR signaling pathway, and KIF20A deletion partially mitigates these effects.\",\n      \"method\": \"Co-immunoprecipitation; western blot of PI3K/AKT/mTOR; siRNA/overexpression; in vitro proliferation/migration assays\",\n      \"journal\": \"Frontiers in endocrinology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP plus pathway readout; single lab, weak evidence\",\n      \"pmids\": [\"40600015\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DEPDC1 is a nuclear/centrosomal protein that is highly expressed in mitosis (with isoform a localizing to the centrosome in a Ser110 phosphorylation-dependent manner and isoform b to the cell cortex), regulates mitotic progression and centrosome integrity, promotes cancer cell proliferation by interacting with ZNF224 to repress the NF-κB inhibitor A20, interacts with E2F1 and FOXM1 to activate proliferative transcriptional programs, acts upstream of a LET-99/GPA-11/JNK pathway to mediate anti-tubulin drug-induced MCL1 degradation and apoptosis, and engages multiple oncogenic signaling axes (NF-κB, Wnt/β-catenin, RAS-ERK, JNK, AKT/mTOR/HIF1α, Hippo) in diverse cancer contexts.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DEPDC1 is a mitosis-associated nuclear and centrosomal protein that functions as a transcriptional co-regulator and signaling scaffold essential for cell proliferation, mitotic spindle integrity, and multiple oncogenic pathways. During mitosis, phosphorylation of DEPDC1 isoform a at Ser110 directs it to the centrosome, where it maintains centrosome integrity and bipolar spindle organization; its depletion causes multipolar spindles, mitotic arrest, and multinucleation [PMID:28602627, PMID:25902835]. DEPDC1 interacts with the zinc-finger repressor ZNF224 to silence the NF-κB inhibitor A20, thereby sustaining NF-κB signaling, and forms a positive-feedback loop with FOXM1 to promote FOXM1 nuclear translocation and transcriptional activity, while also engaging E2F1 to drive G1-S progression [PMID:20587513, PMID:39004911, PMID:28634077]. DEPDC1 additionally activates Wnt/β-catenin, JNK, RAS-ERK, and AKT/mTOR/HIF1α pathways across multiple tumor types, coupling proliferative signaling to drug resistance, glycolysis, and anti-tubulin drug-induced apoptosis via JNK-dependent MCL1 degradation [PMID:25064737, PMID:34268303, PMID:39068164].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Establishing that DEPDC1 is required for bladder cancer cell proliferation and localizes to the nucleus answered the basic question of whether this uncharacterized DEP-domain protein has oncogenic relevance.\",\n      \"evidence\": \"siRNA knockdown with growth inhibition readout; immunocytochemistry in bladder cancer cells\",\n      \"pmids\": [\"17452976\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular mechanism or interacting partner identified\", \"Single cancer type tested\", \"No mitotic role yet recognized\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identification of ZNF224 as a DEPDC1 binding partner and A20 as a transcriptional target established the first mechanism: DEPDC1 co-represses A20 to sustain NF-κB signaling, and disrupting this interaction triggers apoptosis.\",\n      \"evidence\": \"Reciprocal Co-IP; cell-permeable peptide disruption; in vitro and in vivo apoptosis rescue\",\n      \"pmids\": [\"20587513\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How DEPDC1-ZNF224 is recruited to the A20 promoter is unknown\", \"Whether this mechanism operates outside bladder cancer is untested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Cross-species genetic epistasis revealed that DEPDC1/LET-99 acts upstream of a heterotrimeric G-protein (GPA-11) to activate JNK, linking DEPDC1 to anti-tubulin drug-induced MCL1 degradation and apoptosis — the first non-transcriptional signaling axis for DEPDC1.\",\n      \"evidence\": \"C. elegans RNAi screen and epistasis; human cell JNK inhibition and MCL1 degradation assays\",\n      \"pmids\": [\"25064737\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical interaction between DEPDC1 and G-protein subunits not shown in human cells\", \"Whether DEPDC1's DEP domain mediates G-protein coupling is unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstrating that DEPDC1 expression peaks in mitosis and that its knockdown causes multipolar spindles and multinucleation established DEPDC1 as a bona fide mitotic regulator, not merely a proliferation-associated gene.\",\n      \"evidence\": \"Synchronized cell expression profiling; immunofluorescence of mitotic defects upon siRNA depletion\",\n      \"pmids\": [\"25902835\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which DEPDC1 maintains spindle bipolarity unknown\", \"No centrosomal localization yet determined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Mapping Ser110 phosphorylation as essential for centrosomal targeting of isoform a, and distinguishing cortical localization of isoform b, provided the first post-translational mechanism controlling DEPDC1 function and explained its role in centrosome integrity.\",\n      \"evidence\": \"Mass spectrometry; phospho-mutant rescue; immunofluorescence of isoform-specific localization\",\n      \"pmids\": [\"28602627\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for Ser110 phosphorylation not identified\", \"Centrosomal substrates or effectors of DEPDC1 unknown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showing DEPDC1 interacts with E2F1 and enhances its transcriptional activity broadened DEPDC1's role from NF-κB co-repressor to a more general transcriptional co-activator promoting G1-S transition.\",\n      \"evidence\": \"Co-IP; E2F reporter assay; cell cycle analysis; xenograft in prostate cancer\",\n      \"pmids\": [\"28634077\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether DEPDC1 binds E2F1 directly or through a complex is unresolved\", \"Genome-wide E2F1 target effects not mapped\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"DEPDC1 was connected to JNK-dependent chemoresistance in HCC and to CCL20/CCR6-mediated angiogenesis, revealing tissue-specific downstream effectors beyond NF-κB.\",\n      \"evidence\": \"JNK inhibitor reversal of DEPDC1 overexpression effects; CCL20/CCR6 siRNA rescue; in vitro angiogenesis\",\n      \"pmids\": [\"31189746\", \"31322256\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding to JNK pathway components not demonstrated\", \"Whether CCL20 regulation is transcriptional or post-transcriptional unclear\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"DEPDC1 was placed downstream of ALPK2 kinase and upstream of Wnt/β-catenin-driven EMT, and its mRNA was shown to be stabilized by lncRNA linc-ROR via HNRNPK, establishing both upstream regulators and a key oncogenic effector pathway.\",\n      \"evidence\": \"Co-IP and rescue epistasis for ALPK2; lentiviral manipulation with in vivo metastasis imaging for Wnt axis; RIP for HNRNPK-mediated mRNA stabilization\",\n      \"pmids\": [\"34210956\", \"34268303\", \"34741030\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether ALPK2 directly phosphorylates DEPDC1 is unknown\", \"Mechanism by which DEPDC1 engages Wnt1/β-catenin not defined at protein level\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Discovery of the DEPDC1-FOXM1 physical interaction and transcriptional repression of DEPDC1 by FOXO3a established transcription factor partnerships and a negative regulatory input, while also reinforcing Wnt/β-catenin as a shared downstream axis.\",\n      \"evidence\": \"Co-IP and colocalization for FOXM1; dual-luciferase promoter assay for FOXO3a; Wnt pathway reporter\",\n      \"pmids\": [\"36072787\", \"35795985\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"FOXM1-DEPDC1 stoichiometry and domain requirements undefined\", \"FOXO3a regulation not confirmed outside nephroblastoma\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A FOXM1-DEPDC1 positive feedback loop was demonstrated: FOXM1 transcriptionally induces DEPDC1 via promoter binding, while DEPDC1 reciprocally promotes FOXM1 nuclear translocation and activity, providing the first self-reinforcing circuit for DEPDC1 in hepatocarcinogenesis.\",\n      \"evidence\": \"ChIP; reciprocal Co-IP; nuclear fractionation; siRNA rescue; luciferase reporter\",\n      \"pmids\": [\"39004911\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the feedback loop operates in non-hepatic cancers is unknown\", \"Whether DEPDC1 directly chaperones FOXM1 or acts via an intermediary is unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"DEPDC1 was linked to metabolic reprogramming: it promotes glycolysis through AKT/mTOR/HIF1α and confers TKI resistance in renal cell carcinoma, expanding its role beyond proliferation to metabolic control.\",\n      \"evidence\": \"RNA-seq; non-targeted metabolomics; AKT/mTOR/HIF1α western blot; TKI resistance assays\",\n      \"pmids\": [\"39068164\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct interaction with AKT or mTOR not shown\", \"Metabolic targets of HIF1α downstream of DEPDC1 not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Translational and post-transcriptional regulation of DEPDC1 was further defined: METTL5-mediated 18S rRNA m6A methylation enhances DEPDC1 mRNA translation, and the DUXAP8 lncRNA stabilizes DEPDC1 mRNA via HNRNPF and miR-7-5p sponging.\",\n      \"evidence\": \"m6A modification and translation assays for METTL5; RIP for HNRNPF; miRNA sponge luciferase reporter\",\n      \"pmids\": [\"40018408\", \"39992478\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether METTL5-mediated regulation is DEPDC1-selective or part of global translational control unknown\", \"Relative contribution of miRNA sponging versus HNRNPF-mediated stabilization not quantified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key mechanistic questions remain: the kinase phosphorylating Ser110, the structural basis of DEPDC1's DEP domain interactions, and whether DEPDC1 possesses intrinsic enzymatic activity or functions solely as a scaffold/co-regulator.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No crystal or cryo-EM structure available\", \"DEP domain function not dissected biochemically\", \"No unbiased proteomics of DEPDC1 interactome reported\", \"Whether DEPDC1 has catalytic activity (e.g. GAP activity) is untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 5, 6, 14, 18]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 8, 9, 16]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 14, 18]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 18]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3, 4, 5]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 2, 6, 8, 9, 11, 13, 14, 16, 19]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 7, 11, 19]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 5, 18]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ZNF224\", \"FOXM1\", \"E2F1\", \"KIF4A\", \"ALPK2\", \"KIF20A\", \"S100A16\"],\n    \"other_free_text\": []\n  }\n}\n```"}