{"gene":"DEPDC1B","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2014,"finding":"DEPDC1B functions as an inhibitor of a RhoA-based signaling complex that assembles on the FA-associated protein PTPRF. By competing with RhoA for interaction with PTPRF, DEPDC1B promotes dismantling of focal adhesions, which is necessary for morphological changes preceding mitosis. DEPDC1B accumulates in G2 and coordinates de-adhesion events with cell-cycle progression at mitosis.","method":"Co-immunoprecipitation, competition binding assays, siRNA knockdown with mitotic phenotype readout, live imaging, zebrafish developmental model","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP establishing DEPDC1B-PTPRF-RhoA complex, competition assay, clean KD with defined cellular phenotype, validated in zebrafish in vivo","pmids":["25458010"],"is_preprint":false},{"year":2014,"finding":"DEPDC1B activates Wnt/β-catenin signaling to enhance migration and invasion of non-small cell lung cancer cells; depletion of TCF4 or LEF1 abrogated the biological effects of DEPDC1B on migration and invasion.","method":"Ectopic expression and siRNA knockdown, migration/invasion assays, epistasis via TCF4/LEF1 depletion","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, functional rescue epistasis experiment but no direct biochemical demonstration of β-catenin binding or activation mechanism","pmids":["24971537"],"is_preprint":false},{"year":2014,"finding":"DEPDC1B acts as a guanine nucleotide exchange factor (GEF), promotes Rac1 translocation to the cell membrane, regulates Rac1 activation, and drives cell migration and invasion via a DEPDC1B-Rac1-ERK1/2 signaling axis in oral cancer cells.","method":"GEF activity assay, Rac1 membrane fractionation/translocation assay, siRNA knockdown with migration/invasion readout, ERK1/2 phosphorylation western blot","journal":"Journal of biomedical science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — GEF activity assay plus subcellular fractionation and downstream signaling readout, single lab","pmids":["25091805"],"is_preprint":false},{"year":2015,"finding":"The GAP domain of DEPDC1B interacts with nucleotide-bound forms of RAC1 in vitro and suppresses RAC1 activation, interfering with actin polymerization induced by the GEF TRIO. DEPDC1B also interacts with signaling molecules U2af2, Erh, and Salm. Pitx2 transcriptionally represses DEPDC1B by recruiting HDAC1 to the first intron of the DEPDC1B gene.","method":"In vitro binding assay (GAP domain–RAC1), RAC1 activation assay, actin polymerization assay, chromatin immunoprecipitation (ChIP), luciferase reporter assay, RNAi depletion of Pitx2","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro GAP-RAC1 binding, RAC1 activation assay, ChIP with functional reporter; single lab","pmids":["25704760"],"is_preprint":false},{"year":2020,"finding":"DEPDC1B binds to Rac1 and activates the Rac1-PAK1 pathway to induce EMT and enhance proliferation of prostate cancer cells; this oncogenic effect is reversed by a Rac1-GTP inhibitor or Rac1 knockdown.","method":"Co-immunoprecipitation (DEPDC1B–Rac1), Rac1 activation assay, PAK1 phosphorylation western blot, Rac1 inhibitor rescue, siRNA knockdown, in vivo xenograft","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, pharmacological and genetic rescue experiments, in vivo validation; single lab","pmids":["33135357"],"is_preprint":false},{"year":2020,"finding":"DEPDC1B promotes migration and invasion in pancreatic cancer by interacting with Rac1 and activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway; Rac1 inhibition suppressed DEPDC1B-induced migration in vitro and liver metastasis in vivo.","method":"Co-immunoprecipitation (DEPDC1B–Rac1), western blotting for pathway components (PAK1, LIMK1, cofilin1 phosphorylation), wound healing/Transwell assay, Rac1 inhibitor rescue, in vivo liver metastasis model","journal":"OncoTargets and therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, downstream pathway western blot, pharmacological rescue, in vivo model; single lab","pmids":["32110046"],"is_preprint":false},{"year":2020,"finding":"DEPDC1B promotes bladder cancer cell growth through SHC1: knockdown of SHC1 in DEPDC1B-overexpressed cells abolished DEPDC1B-induced promotion effects, placing SHC1 downstream of DEPDC1B.","method":"siRNA knockdown, overexpression, epistasis rescue experiment (SHC1 KD in DEPDC1B-OE cells), in vivo xenograft","journal":"Cell death & disease","confidence":"Low","confidence_rationale":"Tier 3 / Weak — epistasis by knockdown rescue only, no direct binding or biochemical mechanism shown, single lab","pmids":["33203836"],"is_preprint":false},{"year":2019,"finding":"DEPDC1B drives myoblast proliferation and prevents premature myogenic differentiation independently of canonical WNT/β-catenin signaling; co-knockdown of DEPDC1B and RHOA had an additive effect on reducing proliferation and enhancing differentiation, suggesting they act in parallel rather than in the same pathway in myoblasts.","method":"siRNA knockdown (single and combinatorial), RT-qPCR, immunolabelling, cell cycle regulator expression analysis (cyclins, CDKs, CDKIs)","journal":"Cell proliferation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via combinatorial knockdown with defined differentiation phenotype, two orthogonal pathway controls (WNT and RHOA), single lab","pmids":["31825138"],"is_preprint":false},{"year":2022,"finding":"DEPDC1B competitively associates with ubiquitin ligase CDC16 to prevent SCUBE3 from undergoing ubiquitin-proteasome-mediated degradation, thereby stabilizing secreted SCUBE3 and promoting melanoma angiogenesis and metastasis. This mechanism is downstream of the transcription factor SOX10, which directly activates DEPDC1B expression.","method":"Co-immunoprecipitation (DEPDC1B–CDC16), ubiquitination assay, SCUBE3 stability assay (proteasome inhibitor), siRNA/overexpression functional assays, tissue microarray, in vivo angiogenesis and metastasis models","journal":"Advanced science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, ubiquitination assay, protein stability rescue, in vivo validation, multiple orthogonal methods in one study","pmids":["35088579"],"is_preprint":false},{"year":2021,"finding":"DEPDC1B interacts with CDK1 and its knockdown inhibits HCC progression; CDK1 overexpression rescues the inhibitory effects of DEPDC1B knockdown, placing CDK1 downstream of DEPDC1B in hepatocellular carcinoma.","method":"Co-immunoprecipitation, human GeneChip profiling to identify CDK1 as downstream target, CDK1 overexpression rescue experiment, in vivo xenograft","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus epistasis rescue; single lab, two methods","pmids":["34032605"],"is_preprint":false},{"year":2021,"finding":"DEPDC1B regulates chordoma progression through UBE2T-mediated ubiquitination of BIRC5 (Survivin): DEPDC1B interacts with UBE2T by Co-IP, and BIRC5 overexpression rescues the inhibitory effects of DEPDC1B knockdown.","method":"RNA sequencing, Co-immunoprecipitation (DEPDC1B–UBE2T), BIRC5 overexpression rescue, in vivo xenograft","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, transcriptomics, genetic rescue; single lab","pmids":["34330893"],"is_preprint":false},{"year":2022,"finding":"DEPDC1B promotes cholangiocarcinoma by enhancing the protein stability of CDK1 through the ubiquitin-proteasome system; DEPDC1B knockdown leads to decreased CDK1 protein stability, and CDK1 knockdown weakens DEPDC1B-overexpression-driven CCA promotion.","method":"Gene profiling, western blotting for CDK1 stability with proteasome inhibitor, epistasis via CDK1 knockdown in DEPDC1B-OE cells, in vivo xenograft","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — protein stability assay with proteasome pathway, epistasis rescue; single lab","pmids":["36568241"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B mediates deubiquitination of β-catenin via USP5 to activate Wnt/β-catenin signaling and promote breast cancer invasion and migration; DEPDC1B, USP5, and β-catenin form a protein complex identified by mass spectrometry and confirmed by Co-IP and ubiquitination assay.","method":"Mass spectrometry, Co-immunoprecipitation (DEPDC1B–USP5–β-catenin), ubiquitination assay, siRNA knockdown, in vivo metastasis model","journal":"American journal of physiology. Cell physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS plus Co-IP plus ubiquitination assay, multiple orthogonal methods; single lab","pmids":["37642235"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B interacts with GABRD (GABA receptor delta subunit) in esophageal squamous cell carcinoma; GABRD knockdown partially reverses DEPDC1B-driven ESCC progression, and GABRD regulates ESCC progression through the PI3K/AKT/mTOR pathway.","method":"Co-immunoprecipitation (DEPDC1B–GABRD), shRNA knockdown epistasis, western blotting for PI3K/AKT/mTOR components","journal":"Cancer cell international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP and partial epistasis rescue, single lab, no biochemical mechanism of interaction defined","pmids":["35706026"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B promotes proliferation of epithelial ovarian cancer cells by enhancing AKT phosphorylation at Ser473; this effect is suppressed by AKT inhibitors MK2206 and LY294002.","method":"DEPDC1B overexpression, western blotting for pAKT-Ser473, pharmacological inhibition with MK2206 and LY294002, proliferation assay","journal":"Journal of Cancer","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, phosphorylation western blot plus pharmacological inhibition without direct mechanistic link identified","pmids":["37056386"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B interacts with NUP37 (nucleoporin 37) and activates PI3K/AKT signaling in colorectal cancer; NUP37 overexpression rescues the inhibitory effects of DEPDC1B silencing, placing NUP37 downstream of DEPDC1B.","method":"Co-immunoprecipitation (DEPDC1B–NUP37), western blotting for PI3K/AKT pathway, NUP37 overexpression rescue, in vivo xenograft","journal":"Molecular medicine reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP and epistasis rescue; single lab, no direct biochemical mechanism","pmids":["37203403"],"is_preprint":false},{"year":2022,"finding":"DEPDC1B interacts with KIF23 in hepatocellular carcinoma; KIF23 overexpression reverses the inhibitory effects of DEPDC1B knockdown and suppresses p53 signaling pathway activation, placing KIF23 downstream of DEPDC1B to mediate its effects via p53.","method":"Co-immunoprecipitation (DEPDC1B–KIF23), KIF23 overexpression rescue, western blotting for p53 pathway proteins","journal":"Bioengineered","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP and rescue experiment; database-driven target identification, single lab","pmids":["34983303"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B N-terminus binds to the p85 subunit of PI3K, and DEPDC1B overexpression results in decreased ligand-stimulated tyrosine phosphorylation of p85 and downregulation of pAKT1. DEPDC1B knockdown is associated with downregulation of ligand-stimulated pERK expression, identifying DEPDC1B as a cross-regulator of AKT1 and ERK pathways.","method":"Co-immunoprecipitation (DEPDC1B N-terminus–p85 PI3K), western blotting for pAKT1 and pERK upon ligand stimulation, siRNA knockdown","journal":"Methods in molecular biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, Co-IP and western blot for pathway readouts; abstract does not describe rigorous reconstitution or mutagenesis","pmids":["37191806"],"is_preprint":false},{"year":2020,"finding":"DEPDC1B activates the Akt/GSK3β/Snail signaling pathway to induce EMT and promote migration and invasion in pancreatic ductal adenocarcinoma; DEPDC1B overexpression induced EMT markers detectable by western blotting and immunofluorescence.","method":"Overexpression and siRNA knockdown, western blotting and immunofluorescence for EMT markers and pAkt/pGSK3β/Snail, migration/invasion assays","journal":"Oncology letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — western blot pathway analysis without direct binding evidence; single lab, single method type","pmids":["32934714"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B promotes multiple myeloma progression by upregulating CCNB1 (Cyclin B1) and inhibiting p53 signaling; CCNB1 knockdown partially phenocopies DEPDC1B depletion, and CCNB1 is identified as a putative downstream target co-expressed with DEPDC1B.","method":"siRNA knockdown, overexpression, flow cytometry for cell cycle/apoptosis, western blotting for p53 pathway, in vivo xenograft, co-expression analysis","journal":"Tissue & cell","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-expression and functional knockdown without direct protein interaction assay; single lab","pmids":["37979396"],"is_preprint":false},{"year":2023,"finding":"XTP1 (DEPDC1B) activates CDK6 in gastric cancer: XTP1 knockdown inhibits CDK6 expression and CDK6 knockdown abates the proliferative promotion induced by XTP1 overexpression, placing CDK6 downstream of XTP1.","method":"Lentiviral overexpression and knockdown, human GeneChip assay, RT-qPCR, western blotting, CDK6 knockdown rescue experiment, cell cycle and apoptosis assays","journal":"Annals of translational medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — epistasis by rescue only, no direct protein interaction demonstrated; single lab","pmids":["36819538"],"is_preprint":false},{"year":2024,"finding":"TFDP1 transcriptionally activates DEPDC1B expression; ZNF146 knockdown reduces TFDP1 transcription, decreasing DEPDC1B levels and causing G2/M arrest in ovarian cancer cells. Ectopic DEPDC1B expression rescues tumor progression inhibited by ZNF146 knockdown, placing DEPDC1B downstream of the ZNF146/TFDP1 transcriptional axis.","method":"ChIP or transcriptional reporter for TFDP1 binding to DEPDC1B promoter (implied), siRNA combinatorial knockdown, DEPDC1B overexpression rescue, flow cytometry for cell cycle, in vivo xenograft","journal":"Reproduction","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional epistasis, abstract does not detail direct binding assay; single lab","pmids":["38614125"],"is_preprint":false},{"year":2025,"finding":"EBF1 transcriptionally represses DEPDC1B in colon adenocarcinoma; EBF1 loss (due to promoter hypermethylation) leads to DEPDC1B transcriptional activation, driving cell cycle progression and EMT. EBF1 overexpression reduces DEPDC1B expression, and DEPDC1B restoration negates EBF1's tumor-suppressive effects.","method":"siRNA knockdown and overexpression epistasis, 5-azacytidine treatment restoring EBF1, RT-qPCR and western blotting, isograft tumor models","journal":"Biochemical genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional epistasis and methylation rescue; no direct ChIP or binding assay described in abstract; single lab","pmids":["41402613"],"is_preprint":false}],"current_model":"DEPDC1B is a DEP- and RhoGAP-domain-containing protein that accumulates in G2/M and coordinates focal adhesion dismantling with mitotic entry by competing with RhoA for binding to PTPRF; it activates Rac1 (acting as a GEF or GEF-like activator in some contexts while its GAP domain can suppress RAC1 in others), engages the Rac1-PAK1-LIMK1-cofilin1 axis to promote cell migration and invasion, stabilizes pro-tumorigenic proteins (SCUBE3, CDK1, CCNB1) by sequestering ubiquitin-pathway components (CDC16, UBE2T), facilitates β-catenin stability via USP5-mediated deubiquitination to activate Wnt signaling, and modulates PI3K/AKT and ERK pathways at least in part through interaction with the p85 PI3K subunit, collectively placing DEPDC1B at the nexus of cytoskeletal remodeling, cell-cycle progression, and oncogenic signaling."},"narrative":{"mechanistic_narrative":"DEPDC1B is a DEP- and RhoGAP-domain protein that couples cytoskeletal remodeling to cell-cycle progression and acts as a broadly oncogenic effector across multiple carcinomas [PMID:25458010, PMID:25091805]. Its founding role is to coordinate de-adhesion with mitotic entry: it accumulates in G2 and inhibits a RhoA-based signaling complex by competing with RhoA for binding to the focal-adhesion protein PTPRF, thereby promoting focal-adhesion dismantling ahead of mitosis [PMID:25458010]. DEPDC1B regulates Rho-family GTPase output, both binding and activating Rac1 to drive its membrane translocation and engage the Rac1–PAK1–LIMK1–cofilin1 axis that promotes migration, invasion, and EMT [PMID:25091805, PMID:33135357, PMID:32110046]; its GAP domain conversely binds nucleotide-bound RAC1 and can suppress RAC1 activation and TRIO-induced actin polymerization, indicating context-dependent control of Rac1 [PMID:25704760]. Beyond cytoskeletal signaling, DEPDC1B stabilizes pro-tumorigenic proteins by sequestering ubiquitin-pathway components—competing with the ubiquitin ligase CDC16 to protect SCUBE3 from proteasomal degradation and promote melanoma angiogenesis and metastasis [PMID:35088579]—and promotes Wnt/β-catenin signaling, in part through a DEPDC1B–USP5–β-catenin complex that deubiquitinates β-catenin to enhance breast cancer invasion [PMID:24971537, PMID:37642235]. Its expression is set by transcription factors that activate (SOX10) or repress (Pitx2 via HDAC1 recruitment) the gene [PMID:25704760, PMID:35088579]. DEPDC1B also drives myoblast proliferation and restrains premature myogenic differentiation, acting in parallel to RHOA and independently of canonical Wnt/β-catenin in that setting [PMID:31825138].","teleology":[{"year":2014,"claim":"Established the founding mechanism: how a cell links focal-adhesion disassembly to mitotic timing, answered by showing DEPDC1B competes with RhoA at PTPRF to dismantle adhesions during G2/M.","evidence":"Reciprocal Co-IP, competition binding, siRNA with mitotic phenotype, live imaging, and zebrafish in vivo model","pmids":["25458010"],"confidence":"High","gaps":["Does not define the structural basis of PTPRF competition","Does not address how G2 accumulation of DEPDC1B is regulated"]},{"year":2014,"claim":"Connected DEPDC1B to oncogenic transcriptional output by showing Wnt/β-catenin (TCF4/LEF1) is required for its migration/invasion effects in NSCLC.","evidence":"Ectopic expression/knockdown with TCF4/LEF1 epistasis, migration/invasion assays","pmids":["24971537"],"confidence":"Medium","gaps":["No direct demonstration of β-catenin binding or the biochemical activation mechanism"]},{"year":2014,"claim":"Defined DEPDC1B as a positive regulator of Rac1, identifying GEF activity, Rac1 membrane translocation, and a downstream ERK1/2 axis driving migration.","evidence":"GEF activity assay, Rac1 membrane fractionation, knockdown with migration readout, pERK1/2 western","pmids":["25091805"],"confidence":"Medium","gaps":["GEF activity not reconciled with later GAP-domain RAC1 suppression data","Single lab"]},{"year":2015,"claim":"Revealed the opposite, GAP-side activity—the DEPDC1B GAP domain binds nucleotide-bound RAC1 and suppresses RAC1 activation—and identified Pitx2/HDAC1 transcriptional repression, framing DEPDC1B as a context-dependent Rac1 regulator under transcriptional control.","evidence":"In vitro GAP-RAC1 binding, RAC1 activation and actin polymerization assays, ChIP and luciferase reporter, Pitx2 RNAi","pmids":["25704760"],"confidence":"Medium","gaps":["Does not resolve when DEPDC1B acts as activator versus suppressor of RAC1","Additional partners (U2af2, Erh, Salm) lack functional follow-up"]},{"year":2019,"claim":"Extended DEPDC1B beyond cancer, showing it drives myoblast proliferation and blocks premature differentiation in parallel to RHOA and independently of canonical Wnt.","evidence":"Single and combinatorial siRNA knockdown, RT-qPCR, immunolabelling, cell-cycle regulator profiling","pmids":["31825138"],"confidence":"Medium","gaps":["Mechanism distinguishing RHOA-parallel action from the PTPRF/RhoA axis not defined"]},{"year":2020,"claim":"Consolidated the Rac1 effector model across prostate and pancreatic cancers, showing DEPDC1B binds Rac1 and activates the PAK1–LIMK1–cofilin1 cascade to drive EMT, migration, and metastasis.","evidence":"Co-IP, Rac1 activation assays, pathway westerns, Rac1 inhibitor/knockdown rescue, in vivo xenograft and liver-metastasis models","pmids":["33135357","32110046"],"confidence":"Medium","gaps":["Does not address GEF-versus-GAP duality observed in earlier work","Direct effect on Rac1 nucleotide state not measured in these systems"]},{"year":2022,"claim":"Identified a non-GTPase mechanism: DEPDC1B competes with the ubiquitin ligase CDC16 to stabilize secreted SCUBE3, linking it to angiogenesis and metastasis downstream of SOX10.","evidence":"Reciprocal Co-IP, ubiquitination and protein-stability assays, in vivo angiogenesis/metastasis models","pmids":["35088579"],"confidence":"High","gaps":["Generality of the ligase-sequestration mechanism to other substrates not established"]},{"year":2023,"claim":"Demonstrated DEPDC1B promotes β-catenin stability through a DEPDC1B–USP5–β-catenin complex that deubiquitinates β-catenin, providing a biochemical basis for its Wnt activation.","evidence":"Mass spectrometry, Co-IP, ubiquitination assay, siRNA knockdown, in vivo metastasis model","pmids":["37642235"],"confidence":"Medium","gaps":["Whether USP5 recruitment is direct or requires bridging factors unresolved","Single lab"]},{"year":2023,"claim":"Mapped DEPDC1B onto PI3K/AKT and ERK signaling, with the N-terminus binding the p85 PI3K subunit and modulating ligand-stimulated pAKT1 and pERK.","evidence":"Co-IP of DEPDC1B N-terminus with p85, pAKT1/pERK westerns on ligand stimulation, knockdown","pmids":["37191806"],"confidence":"Low","gaps":["No reconstitution or mutagenesis defining the p85-binding interface","Directionality of AKT regulation appears inconsistent across cancer contexts"]},{"year":2024,"claim":"Defined transcriptional control of DEPDC1B, with the ZNF146/TFDP1 axis activating it and EBF1 (silenced by promoter hypermethylation) repressing it, linking its dysregulation to G2/M progression and EMT in tumors.","evidence":"Combinatorial knockdown, reporter/methylation studies, DEPDC1B rescue, cell-cycle flow cytometry, in vivo models","pmids":["38614125","41402613"],"confidence":"Low","gaps":["Direct promoter-binding assays not detailed in these reports","Single lab per axis"]},{"year":null,"claim":"How DEPDC1B switches between Rac1-activating (GEF-like) and Rac1-suppressing (GAP) modes, and whether its RhoA/PTPRF de-adhesion role, ubiquitin-pathway sequestration, and PI3K/AKT cross-regulation operate through unified or distinct domains, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model reconciling GEF and GAP activities","Domain requirements for the many reported partners not systematically mapped","Most downstream-target studies rely on epistasis without direct biochemistry"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[2,4,5]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,4,5]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]}],"complexes":[],"partners":["PTPRF","RAC1","CDC16","USP5","CTNNB1","PIK3R1","UBE2T"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WUY9","full_name":"DEP domain-containing protein 1B","aliases":["HBV X-transactivated gene 8 protein","HBV XAg-transactivated protein 8"],"length_aa":529,"mass_kda":61.8,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8WUY9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DEPDC1B","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000035499","cell_line_id":"CID000563","localizations":[{"compartment":"membrane","grade":3},{"compartment":"cytoplasmic","grade":2}],"interactors":[{"gene":"ANAPC4","stoichiometry":0.2},{"gene":"CDC23","stoichiometry":0.2},{"gene":"CDC16","stoichiometry":0.2},{"gene":"YWHAE","stoichiometry":0.2},{"gene":"YWHAZ","stoichiometry":0.2},{"gene":"ANAPC1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000563","total_profiled":1310},"omim":[{"mim_id":"621189","title":"LONG INTERGENIC NONCODING RNA 2525; LINC02525","url":"https://www.omim.org/entry/621189"},{"mim_id":"616073","title":"DEP DOMAIN-CONTAINING PROTEIN 1B; DEPDC1B","url":"https://www.omim.org/entry/616073"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":10.5},{"tissue":"gallbladder","ntpm":19.7},{"tissue":"lymphoid tissue","ntpm":19.3},{"tissue":"testis","ntpm":11.8}],"url":"https://www.proteinatlas.org/search/DEPDC1B"},"hgnc":{"alias_symbol":["XTP1","BRCC3"],"prev_symbol":[]},"alphafold":{"accession":"Q8WUY9","domains":[{"cath_id":"1.10.10.10","chopping":"19-106","consensus_level":"high","plddt":86.6958,"start":19,"end":106},{"cath_id":"1.10.555.10","chopping":"230-398","consensus_level":"high","plddt":89.5896,"start":230,"end":398}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WUY9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WUY9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WUY9-F1-predicted_aligned_error_v6.png","plddt_mean":77.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DEPDC1B","jax_strain_url":"https://www.jax.org/strain/search?query=DEPDC1B"},"sequence":{"accession":"Q8WUY9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WUY9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WUY9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WUY9"}},"corpus_meta":[{"pmid":"25458010","id":"PMC_25458010","title":"DEPDC1B coordinates de-adhesion events and cell-cycle progression at mitosis.","date":"2014","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/25458010","citation_count":78,"is_preprint":false},{"pmid":"24971537","id":"PMC_24971537","title":"DEPDC1B enhances migration and invasion of non-small cell lung cancer cells via activating Wnt/β-catenin signaling.","date":"2014","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/24971537","citation_count":60,"is_preprint":false},{"pmid":"33135357","id":"PMC_33135357","title":"The metastatic promoter DEPDC1B induces epithelial-mesenchymal transition and promotes prostate cancer cell proliferation via Rac1-PAK1 signaling.","date":"2020","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33135357","citation_count":49,"is_preprint":false},{"pmid":"25091805","id":"PMC_25091805","title":"A putative novel protein, DEPDC1B, is overexpressed in oral cancer patients, and enhanced anchorage-independent growth in oral cancer cells that is mediated by Rac1 and ERK.","date":"2014","source":"Journal of biomedical science","url":"https://pubmed.ncbi.nlm.nih.gov/25091805","citation_count":47,"is_preprint":false},{"pmid":"33203836","id":"PMC_33203836","title":"DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/33203836","citation_count":31,"is_preprint":false},{"pmid":"29163701","id":"PMC_29163701","title":"High levels of DEPDC1B predict shorter biochemical recurrence-free survival of patients with prostate cancer.","date":"2017","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/29163701","citation_count":30,"is_preprint":false},{"pmid":"30880030","id":"PMC_30880030","title":"DEPDC1B knockdown inhibits the development of malignant melanoma through suppressing cell proliferation and inducing cell apoptosis.","date":"2019","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/30880030","citation_count":29,"is_preprint":false},{"pmid":"32110046","id":"PMC_32110046","title":"DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32110046","citation_count":29,"is_preprint":false},{"pmid":"34032605","id":"PMC_34032605","title":"Overexpressed DEPDC1B contributes to the progression of hepatocellular carcinoma by CDK1.","date":"2021","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/34032605","citation_count":24,"is_preprint":false},{"pmid":"35088579","id":"PMC_35088579","title":"DEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3.","date":"2022","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/35088579","citation_count":19,"is_preprint":false},{"pmid":"31825138","id":"PMC_31825138","title":"DEPDC1B is a key regulator of myoblast proliferation in mouse and man.","date":"2019","source":"Cell proliferation","url":"https://pubmed.ncbi.nlm.nih.gov/31825138","citation_count":15,"is_preprint":false},{"pmid":"34330893","id":"PMC_34330893","title":"DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/34330893","citation_count":15,"is_preprint":false},{"pmid":"32934714","id":"PMC_32934714","title":"DEPDC1B promotes migration and invasion in pancreatic ductal adenocarcinoma by activating the Akt/GSK3β/Snail pathway.","date":"2020","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/32934714","citation_count":14,"is_preprint":false},{"pmid":"37642235","id":"PMC_37642235","title":"DEPDC1B-mediated USP5 deubiquitination of β-catenin promotes breast cancer metastasis by activating the wnt/β-catenin pathway.","date":"2023","source":"American journal of physiology. Cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/37642235","citation_count":14,"is_preprint":false},{"pmid":"25704760","id":"PMC_25704760","title":"Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2.","date":"2015","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/25704760","citation_count":12,"is_preprint":false},{"pmid":"35706026","id":"PMC_35706026","title":"DEPDC1B collaborates with GABRD to regulate ESCC progression.","date":"2022","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/35706026","citation_count":10,"is_preprint":false},{"pmid":"27034663","id":"PMC_27034663","title":"In Silico Approach for SAR Analysis of the Predicted Model of DEPDC1B: A Novel Target for Oral Cancer.","date":"2016","source":"Advances in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/27034663","citation_count":10,"is_preprint":false},{"pmid":"36016512","id":"PMC_36016512","title":"DEPDC1B promotes colorectal cancer via facilitating cell proliferation and migration while inhibiting apoptosis.","date":"2022","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/36016512","citation_count":9,"is_preprint":false},{"pmid":"37203403","id":"PMC_37203403","title":"DEPDC1B is involved in the proliferation, metastasis, cell cycle arrest and apoptosis of colon cancer cells by regulating NUP37.","date":"2023","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/37203403","citation_count":9,"is_preprint":false},{"pmid":"32684847","id":"PMC_32684847","title":"Knockdown of DEPDC1B inhibits the development of glioblastoma.","date":"2020","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/32684847","citation_count":9,"is_preprint":false},{"pmid":"38614125","id":"PMC_38614125","title":"ZNF146 regulates cell cycle progression via TFDP1 and DEPDC1B in ovarian cancer cells.","date":"2024","source":"Reproduction (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/38614125","citation_count":8,"is_preprint":false},{"pmid":"34983303","id":"PMC_34983303","title":"DEP domain containing 1B (DEPDC1B) exerts the tumor promoter in hepatocellular carcinoma through activating p53 signaling pathway via kinesin family member 23 (KIF23).","date":"2022","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/34983303","citation_count":7,"is_preprint":false},{"pmid":"25458006","id":"PMC_25458006","title":"Arrested detachment: a DEPDC1B-mediated de-adhesion mitotic checkpoint.","date":"2014","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/25458006","citation_count":7,"is_preprint":false},{"pmid":"37742812","id":"PMC_37742812","title":"Platycodin D inhibits glioblastoma cell proliferation, migration, and invasion by regulating DEPDC1B-mediated epithelial-to-mesenchymal transition.","date":"2023","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/37742812","citation_count":5,"is_preprint":false},{"pmid":"37056386","id":"PMC_37056386","title":"Role of DEP domain-containing protein 1B (DEPDC1B) in epithelial ovarian cancer.","date":"2023","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/37056386","citation_count":3,"is_preprint":false},{"pmid":"36913076","id":"PMC_36913076","title":"Circ_0005276 Promotes Prostate Cancer Progression Through the Crosstalk of miR-128-3p/DEPDC1B Axis.","date":"2023","source":"Biochemical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36913076","citation_count":3,"is_preprint":false},{"pmid":"32147621","id":"PMC_32147621","title":"Establishment of rat anti-canine DEP domain containing 1B (DEPDC1B) monoclonal antibodies.","date":"2020","source":"The Journal of veterinary medical science","url":"https://pubmed.ncbi.nlm.nih.gov/32147621","citation_count":2,"is_preprint":false},{"pmid":"39844908","id":"PMC_39844908","title":"DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure.","date":"2025","source":"Frontiers in cardiovascular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39844908","citation_count":2,"is_preprint":false},{"pmid":"37979396","id":"PMC_37979396","title":"DEPDC1B enhances malignant phenotypes of multiple myeloma through upregulating CCNB1 and inhibiting p53 signaling pathway.","date":"2023","source":"Tissue & cell","url":"https://pubmed.ncbi.nlm.nih.gov/37979396","citation_count":1,"is_preprint":false},{"pmid":"36819538","id":"PMC_36819538","title":"XTP1 facilitates the growth and development of gastric cancer by activating CDK6.","date":"2023","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36819538","citation_count":1,"is_preprint":false},{"pmid":"37191806","id":"PMC_37191806","title":"Illuminating DEPDC1B in Multi-pronged Regulation of Tumor Progression.","date":"2023","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/37191806","citation_count":1,"is_preprint":false},{"pmid":"36568241","id":"PMC_36568241","title":"DEPDC1B promotes development of cholangiocarcinoma through enhancing the stability of CDK1 and regulating malignant phenotypes.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36568241","citation_count":1,"is_preprint":false},{"pmid":"41402613","id":"PMC_41402613","title":"Transcription Activation of DEPDC1B Upon EBF1 Loss Contributes to Cell Cycle Progression and Epithelial-Mesenchymal Transition in Colon Adenocarcinoma.","date":"2025","source":"Biochemical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/41402613","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17982,"output_tokens":5697,"usd":0.0697,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14287,"output_tokens":3563,"usd":0.080255,"stage2_stop_reason":"end_turn"},"total_usd":0.149955,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"DEPDC1B functions as an inhibitor of a RhoA-based signaling complex that assembles on the FA-associated protein PTPRF. By competing with RhoA for interaction with PTPRF, DEPDC1B promotes dismantling of focal adhesions, which is necessary for morphological changes preceding mitosis. DEPDC1B accumulates in G2 and coordinates de-adhesion events with cell-cycle progression at mitosis.\",\n      \"method\": \"Co-immunoprecipitation, competition binding assays, siRNA knockdown with mitotic phenotype readout, live imaging, zebrafish developmental model\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP establishing DEPDC1B-PTPRF-RhoA complex, competition assay, clean KD with defined cellular phenotype, validated in zebrafish in vivo\",\n      \"pmids\": [\"25458010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DEPDC1B activates Wnt/β-catenin signaling to enhance migration and invasion of non-small cell lung cancer cells; depletion of TCF4 or LEF1 abrogated the biological effects of DEPDC1B on migration and invasion.\",\n      \"method\": \"Ectopic expression and siRNA knockdown, migration/invasion assays, epistasis via TCF4/LEF1 depletion\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, functional rescue epistasis experiment but no direct biochemical demonstration of β-catenin binding or activation mechanism\",\n      \"pmids\": [\"24971537\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DEPDC1B acts as a guanine nucleotide exchange factor (GEF), promotes Rac1 translocation to the cell membrane, regulates Rac1 activation, and drives cell migration and invasion via a DEPDC1B-Rac1-ERK1/2 signaling axis in oral cancer cells.\",\n      \"method\": \"GEF activity assay, Rac1 membrane fractionation/translocation assay, siRNA knockdown with migration/invasion readout, ERK1/2 phosphorylation western blot\",\n      \"journal\": \"Journal of biomedical science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — GEF activity assay plus subcellular fractionation and downstream signaling readout, single lab\",\n      \"pmids\": [\"25091805\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The GAP domain of DEPDC1B interacts with nucleotide-bound forms of RAC1 in vitro and suppresses RAC1 activation, interfering with actin polymerization induced by the GEF TRIO. DEPDC1B also interacts with signaling molecules U2af2, Erh, and Salm. Pitx2 transcriptionally represses DEPDC1B by recruiting HDAC1 to the first intron of the DEPDC1B gene.\",\n      \"method\": \"In vitro binding assay (GAP domain–RAC1), RAC1 activation assay, actin polymerization assay, chromatin immunoprecipitation (ChIP), luciferase reporter assay, RNAi depletion of Pitx2\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro GAP-RAC1 binding, RAC1 activation assay, ChIP with functional reporter; single lab\",\n      \"pmids\": [\"25704760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DEPDC1B binds to Rac1 and activates the Rac1-PAK1 pathway to induce EMT and enhance proliferation of prostate cancer cells; this oncogenic effect is reversed by a Rac1-GTP inhibitor or Rac1 knockdown.\",\n      \"method\": \"Co-immunoprecipitation (DEPDC1B–Rac1), Rac1 activation assay, PAK1 phosphorylation western blot, Rac1 inhibitor rescue, siRNA knockdown, in vivo xenograft\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, pharmacological and genetic rescue experiments, in vivo validation; single lab\",\n      \"pmids\": [\"33135357\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DEPDC1B promotes migration and invasion in pancreatic cancer by interacting with Rac1 and activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway; Rac1 inhibition suppressed DEPDC1B-induced migration in vitro and liver metastasis in vivo.\",\n      \"method\": \"Co-immunoprecipitation (DEPDC1B–Rac1), western blotting for pathway components (PAK1, LIMK1, cofilin1 phosphorylation), wound healing/Transwell assay, Rac1 inhibitor rescue, in vivo liver metastasis model\",\n      \"journal\": \"OncoTargets and therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, downstream pathway western blot, pharmacological rescue, in vivo model; single lab\",\n      \"pmids\": [\"32110046\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DEPDC1B promotes bladder cancer cell growth through SHC1: knockdown of SHC1 in DEPDC1B-overexpressed cells abolished DEPDC1B-induced promotion effects, placing SHC1 downstream of DEPDC1B.\",\n      \"method\": \"siRNA knockdown, overexpression, epistasis rescue experiment (SHC1 KD in DEPDC1B-OE cells), in vivo xenograft\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — epistasis by knockdown rescue only, no direct binding or biochemical mechanism shown, single lab\",\n      \"pmids\": [\"33203836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"DEPDC1B drives myoblast proliferation and prevents premature myogenic differentiation independently of canonical WNT/β-catenin signaling; co-knockdown of DEPDC1B and RHOA had an additive effect on reducing proliferation and enhancing differentiation, suggesting they act in parallel rather than in the same pathway in myoblasts.\",\n      \"method\": \"siRNA knockdown (single and combinatorial), RT-qPCR, immunolabelling, cell cycle regulator expression analysis (cyclins, CDKs, CDKIs)\",\n      \"journal\": \"Cell proliferation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via combinatorial knockdown with defined differentiation phenotype, two orthogonal pathway controls (WNT and RHOA), single lab\",\n      \"pmids\": [\"31825138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DEPDC1B competitively associates with ubiquitin ligase CDC16 to prevent SCUBE3 from undergoing ubiquitin-proteasome-mediated degradation, thereby stabilizing secreted SCUBE3 and promoting melanoma angiogenesis and metastasis. This mechanism is downstream of the transcription factor SOX10, which directly activates DEPDC1B expression.\",\n      \"method\": \"Co-immunoprecipitation (DEPDC1B–CDC16), ubiquitination assay, SCUBE3 stability assay (proteasome inhibitor), siRNA/overexpression functional assays, tissue microarray, in vivo angiogenesis and metastasis models\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, ubiquitination assay, protein stability rescue, in vivo validation, multiple orthogonal methods in one study\",\n      \"pmids\": [\"35088579\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DEPDC1B interacts with CDK1 and its knockdown inhibits HCC progression; CDK1 overexpression rescues the inhibitory effects of DEPDC1B knockdown, placing CDK1 downstream of DEPDC1B in hepatocellular carcinoma.\",\n      \"method\": \"Co-immunoprecipitation, human GeneChip profiling to identify CDK1 as downstream target, CDK1 overexpression rescue experiment, in vivo xenograft\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus epistasis rescue; single lab, two methods\",\n      \"pmids\": [\"34032605\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DEPDC1B regulates chordoma progression through UBE2T-mediated ubiquitination of BIRC5 (Survivin): DEPDC1B interacts with UBE2T by Co-IP, and BIRC5 overexpression rescues the inhibitory effects of DEPDC1B knockdown.\",\n      \"method\": \"RNA sequencing, Co-immunoprecipitation (DEPDC1B–UBE2T), BIRC5 overexpression rescue, in vivo xenograft\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, transcriptomics, genetic rescue; single lab\",\n      \"pmids\": [\"34330893\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DEPDC1B promotes cholangiocarcinoma by enhancing the protein stability of CDK1 through the ubiquitin-proteasome system; DEPDC1B knockdown leads to decreased CDK1 protein stability, and CDK1 knockdown weakens DEPDC1B-overexpression-driven CCA promotion.\",\n      \"method\": \"Gene profiling, western blotting for CDK1 stability with proteasome inhibitor, epistasis via CDK1 knockdown in DEPDC1B-OE cells, in vivo xenograft\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — protein stability assay with proteasome pathway, epistasis rescue; single lab\",\n      \"pmids\": [\"36568241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B mediates deubiquitination of β-catenin via USP5 to activate Wnt/β-catenin signaling and promote breast cancer invasion and migration; DEPDC1B, USP5, and β-catenin form a protein complex identified by mass spectrometry and confirmed by Co-IP and ubiquitination assay.\",\n      \"method\": \"Mass spectrometry, Co-immunoprecipitation (DEPDC1B–USP5–β-catenin), ubiquitination assay, siRNA knockdown, in vivo metastasis model\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS plus Co-IP plus ubiquitination assay, multiple orthogonal methods; single lab\",\n      \"pmids\": [\"37642235\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B interacts with GABRD (GABA receptor delta subunit) in esophageal squamous cell carcinoma; GABRD knockdown partially reverses DEPDC1B-driven ESCC progression, and GABRD regulates ESCC progression through the PI3K/AKT/mTOR pathway.\",\n      \"method\": \"Co-immunoprecipitation (DEPDC1B–GABRD), shRNA knockdown epistasis, western blotting for PI3K/AKT/mTOR components\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP and partial epistasis rescue, single lab, no biochemical mechanism of interaction defined\",\n      \"pmids\": [\"35706026\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B promotes proliferation of epithelial ovarian cancer cells by enhancing AKT phosphorylation at Ser473; this effect is suppressed by AKT inhibitors MK2206 and LY294002.\",\n      \"method\": \"DEPDC1B overexpression, western blotting for pAKT-Ser473, pharmacological inhibition with MK2206 and LY294002, proliferation assay\",\n      \"journal\": \"Journal of Cancer\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, phosphorylation western blot plus pharmacological inhibition without direct mechanistic link identified\",\n      \"pmids\": [\"37056386\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B interacts with NUP37 (nucleoporin 37) and activates PI3K/AKT signaling in colorectal cancer; NUP37 overexpression rescues the inhibitory effects of DEPDC1B silencing, placing NUP37 downstream of DEPDC1B.\",\n      \"method\": \"Co-immunoprecipitation (DEPDC1B–NUP37), western blotting for PI3K/AKT pathway, NUP37 overexpression rescue, in vivo xenograft\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP and epistasis rescue; single lab, no direct biochemical mechanism\",\n      \"pmids\": [\"37203403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DEPDC1B interacts with KIF23 in hepatocellular carcinoma; KIF23 overexpression reverses the inhibitory effects of DEPDC1B knockdown and suppresses p53 signaling pathway activation, placing KIF23 downstream of DEPDC1B to mediate its effects via p53.\",\n      \"method\": \"Co-immunoprecipitation (DEPDC1B–KIF23), KIF23 overexpression rescue, western blotting for p53 pathway proteins\",\n      \"journal\": \"Bioengineered\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP and rescue experiment; database-driven target identification, single lab\",\n      \"pmids\": [\"34983303\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B N-terminus binds to the p85 subunit of PI3K, and DEPDC1B overexpression results in decreased ligand-stimulated tyrosine phosphorylation of p85 and downregulation of pAKT1. DEPDC1B knockdown is associated with downregulation of ligand-stimulated pERK expression, identifying DEPDC1B as a cross-regulator of AKT1 and ERK pathways.\",\n      \"method\": \"Co-immunoprecipitation (DEPDC1B N-terminus–p85 PI3K), western blotting for pAKT1 and pERK upon ligand stimulation, siRNA knockdown\",\n      \"journal\": \"Methods in molecular biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, Co-IP and western blot for pathway readouts; abstract does not describe rigorous reconstitution or mutagenesis\",\n      \"pmids\": [\"37191806\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DEPDC1B activates the Akt/GSK3β/Snail signaling pathway to induce EMT and promote migration and invasion in pancreatic ductal adenocarcinoma; DEPDC1B overexpression induced EMT markers detectable by western blotting and immunofluorescence.\",\n      \"method\": \"Overexpression and siRNA knockdown, western blotting and immunofluorescence for EMT markers and pAkt/pGSK3β/Snail, migration/invasion assays\",\n      \"journal\": \"Oncology letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — western blot pathway analysis without direct binding evidence; single lab, single method type\",\n      \"pmids\": [\"32934714\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B promotes multiple myeloma progression by upregulating CCNB1 (Cyclin B1) and inhibiting p53 signaling; CCNB1 knockdown partially phenocopies DEPDC1B depletion, and CCNB1 is identified as a putative downstream target co-expressed with DEPDC1B.\",\n      \"method\": \"siRNA knockdown, overexpression, flow cytometry for cell cycle/apoptosis, western blotting for p53 pathway, in vivo xenograft, co-expression analysis\",\n      \"journal\": \"Tissue & cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-expression and functional knockdown without direct protein interaction assay; single lab\",\n      \"pmids\": [\"37979396\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"XTP1 (DEPDC1B) activates CDK6 in gastric cancer: XTP1 knockdown inhibits CDK6 expression and CDK6 knockdown abates the proliferative promotion induced by XTP1 overexpression, placing CDK6 downstream of XTP1.\",\n      \"method\": \"Lentiviral overexpression and knockdown, human GeneChip assay, RT-qPCR, western blotting, CDK6 knockdown rescue experiment, cell cycle and apoptosis assays\",\n      \"journal\": \"Annals of translational medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — epistasis by rescue only, no direct protein interaction demonstrated; single lab\",\n      \"pmids\": [\"36819538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TFDP1 transcriptionally activates DEPDC1B expression; ZNF146 knockdown reduces TFDP1 transcription, decreasing DEPDC1B levels and causing G2/M arrest in ovarian cancer cells. Ectopic DEPDC1B expression rescues tumor progression inhibited by ZNF146 knockdown, placing DEPDC1B downstream of the ZNF146/TFDP1 transcriptional axis.\",\n      \"method\": \"ChIP or transcriptional reporter for TFDP1 binding to DEPDC1B promoter (implied), siRNA combinatorial knockdown, DEPDC1B overexpression rescue, flow cytometry for cell cycle, in vivo xenograft\",\n      \"journal\": \"Reproduction\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional epistasis, abstract does not detail direct binding assay; single lab\",\n      \"pmids\": [\"38614125\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"EBF1 transcriptionally represses DEPDC1B in colon adenocarcinoma; EBF1 loss (due to promoter hypermethylation) leads to DEPDC1B transcriptional activation, driving cell cycle progression and EMT. EBF1 overexpression reduces DEPDC1B expression, and DEPDC1B restoration negates EBF1's tumor-suppressive effects.\",\n      \"method\": \"siRNA knockdown and overexpression epistasis, 5-azacytidine treatment restoring EBF1, RT-qPCR and western blotting, isograft tumor models\",\n      \"journal\": \"Biochemical genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional epistasis and methylation rescue; no direct ChIP or binding assay described in abstract; single lab\",\n      \"pmids\": [\"41402613\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DEPDC1B is a DEP- and RhoGAP-domain-containing protein that accumulates in G2/M and coordinates focal adhesion dismantling with mitotic entry by competing with RhoA for binding to PTPRF; it activates Rac1 (acting as a GEF or GEF-like activator in some contexts while its GAP domain can suppress RAC1 in others), engages the Rac1-PAK1-LIMK1-cofilin1 axis to promote cell migration and invasion, stabilizes pro-tumorigenic proteins (SCUBE3, CDK1, CCNB1) by sequestering ubiquitin-pathway components (CDC16, UBE2T), facilitates β-catenin stability via USP5-mediated deubiquitination to activate Wnt signaling, and modulates PI3K/AKT and ERK pathways at least in part through interaction with the p85 PI3K subunit, collectively placing DEPDC1B at the nexus of cytoskeletal remodeling, cell-cycle progression, and oncogenic signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DEPDC1B is a DEP- and RhoGAP-domain protein that couples cytoskeletal remodeling to cell-cycle progression and acts as a broadly oncogenic effector across multiple carcinomas [#0, #2]. Its founding role is to coordinate de-adhesion with mitotic entry: it accumulates in G2 and inhibits a RhoA-based signaling complex by competing with RhoA for binding to the focal-adhesion protein PTPRF, thereby promoting focal-adhesion dismantling ahead of mitosis [#0]. DEPDC1B regulates Rho-family GTPase output, both binding and activating Rac1 to drive its membrane translocation and engage the Rac1–PAK1–LIMK1–cofilin1 axis that promotes migration, invasion, and EMT [#2, #4, #5]; its GAP domain conversely binds nucleotide-bound RAC1 and can suppress RAC1 activation and TRIO-induced actin polymerization, indicating context-dependent control of Rac1 [#3]. Beyond cytoskeletal signaling, DEPDC1B stabilizes pro-tumorigenic proteins by sequestering ubiquitin-pathway components—competing with the ubiquitin ligase CDC16 to protect SCUBE3 from proteasomal degradation and promote melanoma angiogenesis and metastasis [#8]—and promotes Wnt/β-catenin signaling, in part through a DEPDC1B–USP5–β-catenin complex that deubiquitinates β-catenin to enhance breast cancer invasion [#1, #12]. Its expression is set by transcription factors that activate (SOX10) or repress (Pitx2 via HDAC1 recruitment) the gene [#3, #8]. DEPDC1B also drives myoblast proliferation and restrains premature myogenic differentiation, acting in parallel to RHOA and independently of canonical Wnt/β-catenin in that setting [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established the founding mechanism: how a cell links focal-adhesion disassembly to mitotic timing, answered by showing DEPDC1B competes with RhoA at PTPRF to dismantle adhesions during G2/M.\",\n      \"evidence\": \"Reciprocal Co-IP, competition binding, siRNA with mitotic phenotype, live imaging, and zebrafish in vivo model\",\n      \"pmids\": [\"25458010\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the structural basis of PTPRF competition\", \"Does not address how G2 accumulation of DEPDC1B is regulated\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected DEPDC1B to oncogenic transcriptional output by showing Wnt/β-catenin (TCF4/LEF1) is required for its migration/invasion effects in NSCLC.\",\n      \"evidence\": \"Ectopic expression/knockdown with TCF4/LEF1 epistasis, migration/invasion assays\",\n      \"pmids\": [\"24971537\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct demonstration of β-catenin binding or the biochemical activation mechanism\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined DEPDC1B as a positive regulator of Rac1, identifying GEF activity, Rac1 membrane translocation, and a downstream ERK1/2 axis driving migration.\",\n      \"evidence\": \"GEF activity assay, Rac1 membrane fractionation, knockdown with migration readout, pERK1/2 western\",\n      \"pmids\": [\"25091805\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"GEF activity not reconciled with later GAP-domain RAC1 suppression data\", \"Single lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed the opposite, GAP-side activity—the DEPDC1B GAP domain binds nucleotide-bound RAC1 and suppresses RAC1 activation—and identified Pitx2/HDAC1 transcriptional repression, framing DEPDC1B as a context-dependent Rac1 regulator under transcriptional control.\",\n      \"evidence\": \"In vitro GAP-RAC1 binding, RAC1 activation and actin polymerization assays, ChIP and luciferase reporter, Pitx2 RNAi\",\n      \"pmids\": [\"25704760\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not resolve when DEPDC1B acts as activator versus suppressor of RAC1\", \"Additional partners (U2af2, Erh, Salm) lack functional follow-up\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extended DEPDC1B beyond cancer, showing it drives myoblast proliferation and blocks premature differentiation in parallel to RHOA and independently of canonical Wnt.\",\n      \"evidence\": \"Single and combinatorial siRNA knockdown, RT-qPCR, immunolabelling, cell-cycle regulator profiling\",\n      \"pmids\": [\"31825138\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism distinguishing RHOA-parallel action from the PTPRF/RhoA axis not defined\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Consolidated the Rac1 effector model across prostate and pancreatic cancers, showing DEPDC1B binds Rac1 and activates the PAK1–LIMK1–cofilin1 cascade to drive EMT, migration, and metastasis.\",\n      \"evidence\": \"Co-IP, Rac1 activation assays, pathway westerns, Rac1 inhibitor/knockdown rescue, in vivo xenograft and liver-metastasis models\",\n      \"pmids\": [\"33135357\", \"32110046\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not address GEF-versus-GAP duality observed in earlier work\", \"Direct effect on Rac1 nucleotide state not measured in these systems\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified a non-GTPase mechanism: DEPDC1B competes with the ubiquitin ligase CDC16 to stabilize secreted SCUBE3, linking it to angiogenesis and metastasis downstream of SOX10.\",\n      \"evidence\": \"Reciprocal Co-IP, ubiquitination and protein-stability assays, in vivo angiogenesis/metastasis models\",\n      \"pmids\": [\"35088579\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality of the ligase-sequestration mechanism to other substrates not established\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated DEPDC1B promotes β-catenin stability through a DEPDC1B–USP5–β-catenin complex that deubiquitinates β-catenin, providing a biochemical basis for its Wnt activation.\",\n      \"evidence\": \"Mass spectrometry, Co-IP, ubiquitination assay, siRNA knockdown, in vivo metastasis model\",\n      \"pmids\": [\"37642235\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether USP5 recruitment is direct or requires bridging factors unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapped DEPDC1B onto PI3K/AKT and ERK signaling, with the N-terminus binding the p85 PI3K subunit and modulating ligand-stimulated pAKT1 and pERK.\",\n      \"evidence\": \"Co-IP of DEPDC1B N-terminus with p85, pAKT1/pERK westerns on ligand stimulation, knockdown\",\n      \"pmids\": [\"37191806\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reconstitution or mutagenesis defining the p85-binding interface\", \"Directionality of AKT regulation appears inconsistent across cancer contexts\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined transcriptional control of DEPDC1B, with the ZNF146/TFDP1 axis activating it and EBF1 (silenced by promoter hypermethylation) repressing it, linking its dysregulation to G2/M progression and EMT in tumors.\",\n      \"evidence\": \"Combinatorial knockdown, reporter/methylation studies, DEPDC1B rescue, cell-cycle flow cytometry, in vivo models\",\n      \"pmids\": [\"38614125\", \"41402613\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Direct promoter-binding assays not detailed in these reports\", \"Single lab per axis\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DEPDC1B switches between Rac1-activating (GEF-like) and Rac1-suppressing (GAP) modes, and whether its RhoA/PTPRF de-adhesion role, ubiquitin-pathway sequestration, and PI3K/AKT cross-regulation operate through unified or distinct domains, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model reconciling GEF and GAP activities\", \"Domain requirements for the many reported partners not systematically mapped\", \"Most downstream-target studies rely on epistasis without direct biochemistry\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [2, 4, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 4, 5]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PTPRF\", \"RAC1\", \"CDC16\", \"USP5\", \"CTNNB1\", \"PIK3R1\", \"UBE2T\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":6,"faith_total":6,"faith_pct":100.0}}