{"gene":"CDCA5","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2019,"finding":"CDCA5 transcription is directly driven by E2F1, as demonstrated by luciferase reporter assay and chromatin immunoprecipitation (ChIP) in hepatocellular carcinoma cells.","method":"Luciferase reporter assay and chromatin immunoprecipitation (ChIP)","journal":"Journal of Cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (luciferase reporter + ChIP) in a single lab establishing direct transcriptional regulation","pmids":["31205541"],"is_preprint":false},{"year":2021,"finding":"SPOP (E3 ubiquitin ligase adaptor) interacts with CDCA5 and promotes its polyubiquitin-dependent proteasomal degradation in a degron-dependent manner; prostate cancer-associated SPOP mutations impair this degradation.","method":"Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown rescue experiments","journal":"Neoplasia (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus ubiquitination assay plus degron-dependency demonstrated, single lab","pmids":["34509929"],"is_preprint":false},{"year":2021,"finding":"CDCA5 depletion in prostate cancer cells leads to G2/M arrest, severe sister chromatid aggregation disturbance, and apoptosis, confirming its role in sister chromatid cohesion maintenance.","method":"shRNA knockdown, flow cytometry, microscopy of sister chromatid phenotypes","journal":"Neoplasia (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined cellular phenotype (G2/M arrest and sister chromatid defect), single lab","pmids":["34509929"],"is_preprint":false},{"year":2022,"finding":"TPI1 interacts with CDCA5 (identified by Co-IP and mass spectrometry) and stabilizes CDCA5 protein; TPI1-mediated stabilization of CDCA5 activates the PI3K/AKT/mTOR pathway to promote breast cancer progression.","method":"Co-immunoprecipitation, mass spectrometric analysis, ubiquitination assay, overexpression/knockdown","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus MS plus ubiquitination assay, single lab","pmids":["35509067"],"is_preprint":false},{"year":2022,"finding":"CDCA5 knockdown downregulates PDS5A expression in breast cancer cells, and overexpression of PDS5A reverses the anti-proliferative and anti-migratory effects of CDCA5 inhibition, placing PDS5A downstream of CDCA5.","method":"shRNA knockdown, PDS5A overexpression rescue, western blot, proliferation/migration assays","journal":"Molecular medicine reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — rescue epistasis experiment in a single lab with no direct binding assay","pmids":["35506437"],"is_preprint":false},{"year":2024,"finding":"CDCA5 promotes binding of transcription factor E2F1 to the FOXM1 promoter, leading to FOXM1 upregulation and activation of the Wnt/β-catenin signaling pathway in breast cancer cells.","method":"Co-IP, ChIP, dual-luciferase reporter assay, FOXM1 knockdown rescue","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — three orthogonal methods (Co-IP, ChIP, luciferase) in single lab","pmids":["38978058"],"is_preprint":false},{"year":2023,"finding":"Transcription factor KLF5 binds to a specific site in the CDCA5 promoter and directly promotes CDCA5 expression in epithelial ovarian cancer cells; KLF5 overexpression rescues the effects of CDCA5 knockdown.","method":"ChIP, promoter binding assay, KLF5 overexpression rescue","journal":"Experimental cell research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — ChIP with rescue experiment, single lab, abstract does not detail orthogonal promoter validation","pmids":["37247719"],"is_preprint":false},{"year":2024,"finding":"CDCA5 interacts with EEF1A1 (Eukaryotic Translation Elongation Factor 1 Alpha 1), identified by Co-IP and LC-MS/MS, and this interaction regulates mTOR signaling to promote clear cell renal cell carcinoma progression.","method":"Co-immunoprecipitation, LC-MS/MS mass spectrometry, knockdown/overexpression","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus MS identification of binding partner, single lab","pmids":["38658931"],"is_preprint":false},{"year":2024,"finding":"CDCA5 promotes invasion and migration of ovarian cancer cells via activation of the TGF-β1/Smad2/3 signaling pathway, as demonstrated by RNA sequencing identifying ECM/TGF pathway enrichment and functional invasion assays.","method":"RNA sequencing, functional invasion/migration assays, pathway inhibitor experiments","journal":"Journal of ovarian research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptomics-informed pathway placement with functional assays, single lab, no direct protein interaction shown","pmids":["38539247"],"is_preprint":false},{"year":2025,"finding":"CDC40 knockdown induces retention of the first intron of CDCA5 pre-mRNA, causing increased unspliced CDCA5 transcript and decreased CDCA5 protein; CDC40 spliceosome interactions were confirmed by protein-protein interaction experiments.","method":"siRNA knockdown, global transcriptional/splicing analysis, RT-PCR for intron retention, protein-protein interaction assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct molecular mechanism (intron retention) demonstrated by multiple methods (splicing analysis + protein interaction mapping), single lab","pmids":["39747150"],"is_preprint":false},{"year":2020,"finding":"CDCA5 promotes cell cycle progression in bladder cancer cells by upregulating CDC2 and Cyclin B1, and activating the PI3K/AKT/mTOR pathway; CDCA5 also regulates apoptosis through the mitochondrial pathway.","method":"shRNA knockdown, overexpression, western blot for cell cycle proteins and pathway components, flow cytometry","journal":"Journal of Cancer","confidence":"Low","confidence_rationale":"Tier 3 / Weak — western blot pathway readouts without direct interaction or epistasis validation, single lab","pmids":["32201512"],"is_preprint":false},{"year":2021,"finding":"CDCA5 knockdown reduces ERK phosphorylation in prostate cancer cells, indicating CDCA5 functions upstream of the ERK signaling pathway to promote proliferation.","method":"shRNA knockdown, western blot for phospho-ERK, proliferation assays in vitro and xenograft","journal":"Oncology reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — western blot phosphorylation readout, single method for pathway placement, single lab; note corrigendum issued for figure assembly error","pmids":["33650660"],"is_preprint":false},{"year":2025,"finding":"CDCA5 interacts with Cyclin A2 (CCNA2) in NSCLC cells, as identified by Co-immunoprecipitation, and modulates CCNA2 expression; berberine treatment reduces both CDCA5 and CCNA2 levels.","method":"Co-immunoprecipitation, western blot, overexpression rescue","journal":"Journal of natural medicines","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP result, single lab, functional context limited to drug treatment context","pmids":["40155519"],"is_preprint":false},{"year":2025,"finding":"CDCA5 knockdown combined with olaparib synergistically suppresses PI3K/AKT/mTOR signaling, activates autophagy, and exacerbates DNA damage in BRCA1-mutated ovarian cancer cells; pharmacological PI3K/AKT/mTOR activation reverses these effects, placing the pathway mechanistically downstream of CDCA5.","method":"siRNA knockdown, CCK-8, immunofluorescence, TEM, western blot, PI3K pathway activator rescue, xenograft model","journal":"Discover oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — pathway rescue experiment in single lab without direct interaction data","pmids":["41026320"],"is_preprint":false}],"current_model":"CDCA5 (sororin) is a regulator of sister chromatid cohesion whose expression is transcriptionally driven by E2F1 (and KLF5 in some contexts), stabilized by TPI1, and targeted for polyubiquitin-dependent proteasomal degradation by the SPOP E3 adaptor; at the molecular level it interacts with EEF1A1 and Cyclin A2, promotes E2F1 binding to the FOXM1 promoter, and modulates CDC2/Cyclin B1 levels and multiple oncogenic kinase cascades (PI3K/AKT/mTOR, ERK, TGF-β1/Smad2/3) to sustain cell cycle progression, suppress apoptosis, and drive cancer cell proliferation and invasion; its pre-mRNA splicing is regulated by the spliceosome component CDC40."},"narrative":{"mechanistic_narrative":"CDCA5 (sororin) is a regulator of sister chromatid cohesion that is essential for orderly cell cycle progression: its depletion causes G2/M arrest, severe sister chromatid aggregation defects, and apoptosis [PMID:34509929]. Its abundance is controlled at multiple levels — transcriptionally it is a direct target of E2F1 [PMID:31205541], while at the protein level it is stabilized by TPI1 [PMID:35509067] and targeted for polyubiquitin-dependent proteasomal degradation by the E3 ubiquitin ligase adaptor SPOP through a degron-dependent mechanism that is impaired by cancer-associated SPOP mutations [PMID:34509929]. Its production is further gated post-transcriptionally by the spliceosome component CDC40, whose loss causes retention of the first CDCA5 intron and reduced CDCA5 protein [PMID:39747150]. Beyond cohesion, CDCA5 physically engages EEF1A1 [PMID:38658931], and acts to promote E2F1 occupancy of the FOXM1 promoter, driving FOXM1 upregulation and Wnt/β-catenin activation [PMID:38978058]. Across cancer contexts these activities converge on sustained proliferation and invasion, with PI3K/AKT/mTOR signaling placed mechanistically downstream of CDCA5 [PMID:35509067, PMID:41026320].","teleology":[{"year":2019,"claim":"Established how CDCA5 expression is driven in proliferating cancer cells by identifying its upstream transcriptional activator, linking it to the E2F cell-cycle program.","evidence":"Luciferase reporter assay and ChIP in hepatocellular carcinoma cells","pmids":["31205541"],"confidence":"Medium","gaps":["Does not address whether E2F1 regulation holds across other tissues","No measurement of how this transcriptional input couples to cohesion function"]},{"year":2020,"claim":"Connected CDCA5 to cell cycle effectors and survival, showing depletion lowers CDC2/Cyclin B1 and PI3K/AKT/mTOR output while engaging the mitochondrial apoptotic pathway.","evidence":"shRNA knockdown/overexpression with western blot and flow cytometry in bladder cancer cells","pmids":["32201512"],"confidence":"Low","gaps":["Western-blot pathway readouts without direct interaction or epistasis","Does not establish whether PI3K/AKT/mTOR effects are direct or secondary to cell-cycle arrest"]},{"year":2021,"claim":"Resolved how CDCA5 protein levels are degraded by identifying SPOP as the E3 adaptor mediating degron-dependent polyubiquitination, and explained how SPOP mutations elevate CDCA5.","evidence":"Reciprocal Co-IP, ubiquitination assay, and degron-dependency rescue in prostate cancer cells","pmids":["34509929"],"confidence":"Medium","gaps":["Specific lysine residues ubiquitinated not mapped","Whether degradation is cell-cycle phase-restricted not addressed"]},{"year":2021,"claim":"Confirmed the cohesion-maintenance function of CDCA5 by defining the cellular consequences of its loss, anchoring its sororin identity.","evidence":"shRNA knockdown with flow cytometry and microscopy of sister chromatid phenotypes in prostate cancer cells","pmids":["34509929"],"confidence":"Medium","gaps":["Molecular partners at the cohesin complex not characterized in this corpus","Does not distinguish direct cohesion role from indirect cell-cycle arrest"]},{"year":2021,"claim":"Placed CDCA5 upstream of ERK signaling, extending its proliferative role beyond the cell-cycle machinery.","evidence":"shRNA knockdown with phospho-ERK western blot, proliferation and xenograft assays in prostate cancer","pmids":["33650660"],"confidence":"Low","gaps":["Single phosphorylation readout for pathway placement","Corrigendum issued for figure assembly error","Mechanism linking CDCA5 to ERK undefined"]},{"year":2022,"claim":"Identified TPI1 as a CDCA5 binding partner that stabilizes the protein, revealing a positive post-translational input that counterbalances SPOP-mediated turnover.","evidence":"Co-IP, mass spectrometry, and ubiquitination assays in breast cancer cells","pmids":["35509067"],"confidence":"Medium","gaps":["Whether TPI1 directly competes with SPOP not tested","Structural basis of the TPI1–CDCA5 interaction unknown"]},{"year":2022,"claim":"Positioned PDS5A downstream of CDCA5 through epistasis, linking CDCA5 to a cohesion-associated effector in proliferation and migration.","evidence":"shRNA knockdown with PDS5A overexpression rescue, western blot and functional assays in breast cancer","pmids":["35506437"],"confidence":"Low","gaps":["No direct binding assay between CDCA5 and PDS5A","Single-lab epistasis only"]},{"year":2023,"claim":"Added KLF5 as a second transcriptional activator of CDCA5, indicating context-dependent upstream control in ovarian cancer.","evidence":"ChIP, promoter binding assay, and KLF5 overexpression rescue in epithelial ovarian cancer cells","pmids":["37247719"],"confidence":"Low","gaps":["Orthogonal promoter validation not detailed","Relationship to E2F1-driven regulation not reconciled"]},{"year":2024,"claim":"Defined a transcriptional output of CDCA5 by showing it promotes E2F1 binding to the FOXM1 promoter, driving FOXM1 and Wnt/β-catenin activation.","evidence":"Co-IP, ChIP, dual-luciferase reporter, and FOXM1 knockdown rescue in breast cancer cells","pmids":["38978058"],"confidence":"Medium","gaps":["How a cohesion protein facilitates E2F1 promoter occupancy mechanistically unclear","Direct CDCA5–E2F1 contact at chromatin not structurally defined"]},{"year":2024,"claim":"Identified EEF1A1 as a direct CDCA5 partner coupling the protein to mTOR signaling in renal cancer, broadening its interactome beyond the cohesion apparatus.","evidence":"Co-IP and LC-MS/MS with knockdown/overexpression in clear cell renal cell carcinoma","pmids":["38658931"],"confidence":"Medium","gaps":["Interaction interface not mapped","Whether EEF1A1 binding is cohesion-independent unknown"]},{"year":2024,"claim":"Linked CDCA5 to invasion via TGF-β1/Smad2/3 signaling, extending its role into metastatic phenotypes.","evidence":"RNA sequencing, invasion/migration assays, and pathway inhibitor experiments in ovarian cancer","pmids":["38539247"],"confidence":"Low","gaps":["No direct protein interaction shown","Pathway placement inferred from transcriptomics"]},{"year":2025,"claim":"Revealed post-transcriptional control of CDCA5 by the spliceosome, showing CDC40 loss causes first-intron retention and reduced CDCA5 protein.","evidence":"siRNA knockdown, splicing analysis, RT-PCR for intron retention, and protein-protein interaction assays","pmids":["39747150"],"confidence":"Medium","gaps":["Whether CDC40 directly binds CDCA5 pre-mRNA not shown","Physiological conditions altering this splicing not defined"]},{"year":2025,"claim":"Identified Cyclin A2 as a CDCA5 partner in lung cancer and connected both to berberine sensitivity, reinforcing CDCA5's cell-cycle interactions.","evidence":"Co-IP, western blot, and overexpression rescue in NSCLC cells","pmids":["40155519"],"confidence":"Low","gaps":["Single Co-IP without reciprocal validation","Functional context limited to drug treatment"]},{"year":2025,"claim":"Demonstrated therapeutic synergy of CDCA5 depletion with olaparib via PI3K/AKT/mTOR suppression, autophagy, and DNA damage, placing the pathway downstream of CDCA5.","evidence":"siRNA knockdown, CCK-8, immunofluorescence, TEM, PI3K pathway activator rescue, and xenograft in BRCA1-mutated ovarian cancer","pmids":["41026320"],"confidence":"Low","gaps":["No direct interaction data","Mechanism linking CDCA5 to DNA damage repair undefined"]},{"year":null,"claim":"How CDCA5's core cohesion function mechanistically connects to the multiple oncogenic signaling cascades (PI3K/AKT/mTOR, ERK, TGF-β1/Smad, Wnt) attributed to it remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of CDCA5 in any complex within this corpus","Whether signaling roles are direct or downstream of cell-cycle arrest unresolved","Direct cohesin-complex partners not characterized in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[5]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2,10]}],"complexes":[],"partners":["SPOP","TPI1","EEF1A1","CCNA2","E2F1","CDC40"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96FF9","full_name":"Sororin","aliases":["Cell division cycle-associated protein 5","p35"],"length_aa":252,"mass_kda":27.6,"function":"Regulator of sister chromatid cohesion in mitosis stabilizing cohesin complex association with chromatin. May antagonize the action of WAPL which stimulates cohesin dissociation from chromatin. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Required for efficient DNA double-stranded break repair","subcellular_location":"Nucleus; Chromosome; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q96FF9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/CDCA5","classification":"Common Essential","n_dependent_lines":1128,"n_total_lines":1208,"dependency_fraction":0.9337748344370861},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"STAG1","stoichiometry":10.0},{"gene":"STAG2","stoichiometry":4.0},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"SMC1A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CDCA5","total_profiled":1310},"omim":[{"mim_id":"618536","title":"CACTIN, SPLICEOSOME C COMPLEX SUBUNIT; CACTIN","url":"https://www.omim.org/entry/618536"},{"mim_id":"610754","title":"WAPL COHESIN RELEASE FACTOR; WAPL","url":"https://www.omim.org/entry/610754"},{"mim_id":"609374","title":"CELL DIVISION CYCLE-ASSOCIATED PROTEIN 5; CDCA5","url":"https://www.omim.org/entry/609374"},{"mim_id":"601644","title":"PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B (B56), BETA; PPP2R5B","url":"https://www.omim.org/entry/601644"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":50.4},{"tissue":"lymphoid tissue","ntpm":25.7},{"tissue":"testis","ntpm":37.1}],"url":"https://www.proteinatlas.org/search/CDCA5"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q96FF9","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96FF9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96FF9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96FF9-F1-predicted_aligned_error_v6.png","plddt_mean":62.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CDCA5","jax_strain_url":"https://www.jax.org/strain/search?query=CDCA5"},"sequence":{"accession":"Q96FF9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96FF9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96FF9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96FF9"}},"corpus_meta":[{"pmid":"29467944","id":"PMC_29467944","title":"Distinct expression of CDCA3, CDCA5, and CDCA8 leads to shorter relapse free survival in breast cancer patient.","date":"2018","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29467944","citation_count":76,"is_preprint":false},{"pmid":"35509067","id":"PMC_35509067","title":"TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer progression by stabilizing CDCA5.","date":"2022","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35509067","citation_count":54,"is_preprint":false},{"pmid":"31205541","id":"PMC_31205541","title":"CDCA5, Transcribed by E2F1, Promotes Oncogenesis by Enhancing Cell Proliferation and Inhibiting Apoptosis via the AKT Pathway in Hepatocellular Carcinoma.","date":"2019","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/31205541","citation_count":51,"is_preprint":false},{"pmid":"32201512","id":"PMC_32201512","title":"CDCA5 functions as a tumor promoter in bladder cancer by dysregulating mitochondria-mediated apoptosis, cell cycle regulation and PI3k/AKT/mTOR pathway activation.","date":"2020","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/32201512","citation_count":36,"is_preprint":false},{"pmid":"29326043","id":"PMC_29326043","title":"Upregulation of CDCA5 promotes gastric cancer malignant progression via influencing cyclin E1.","date":"2018","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/29326043","citation_count":36,"is_preprint":false},{"pmid":"33650660","id":"PMC_33650660","title":"CDCA5 promotes the progression of prostate cancer by affecting the ERK signalling pathway.","date":"2021","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/33650660","citation_count":23,"is_preprint":false},{"pmid":"34509929","id":"PMC_34509929","title":"SPOP promotes CDCA5 degradation to regulate prostate cancer progression via the AKT pathway.","date":"2021","source":"Neoplasia (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/34509929","citation_count":20,"is_preprint":false},{"pmid":"31593490","id":"PMC_31593490","title":"Overexpression of CDCA5, KIF4A, TPX2, and FOXM1 Coregulated Cell Cycle and Promoted Hepatocellular Carcinoma Development.","date":"2019","source":"Journal of computational biology : a journal of computational molecular cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31593490","citation_count":16,"is_preprint":false},{"pmid":"32759885","id":"PMC_32759885","title":"Cyclin-Dependent Kinase 1 (CDK1) is Co-Expressed with CDCA5: Their Functions in Gastric Cancer Cell Line MGC-803.","date":"2020","source":"Medical science monitor : international medical journal of experimental and clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/32759885","citation_count":11,"is_preprint":false},{"pmid":"33770322","id":"PMC_33770322","title":"LINC01515 promotes nasopharyngeal carcinoma progression by serving as a sponge for miR-325 to up-regulate CDCA5.","date":"2021","source":"Journal of molecular histology","url":"https://pubmed.ncbi.nlm.nih.gov/33770322","citation_count":10,"is_preprint":false},{"pmid":"38978058","id":"PMC_38978058","title":"CDCA5 accelerates progression of breast cancer by promoting the binding of E2F1 and FOXM1.","date":"2024","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38978058","citation_count":9,"is_preprint":false},{"pmid":"35993042","id":"PMC_35993042","title":"lncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression.","date":"2022","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/35993042","citation_count":7,"is_preprint":false},{"pmid":"36428736","id":"PMC_36428736","title":"Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/36428736","citation_count":7,"is_preprint":false},{"pmid":"34077004","id":"PMC_34077004","title":"CDCA5 is negatively regulated by miR-326 and boosts ovarian cancer progression.","date":"2021","source":"Journal of B.U.ON. : official journal of the Balkan Union of Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/34077004","citation_count":7,"is_preprint":false},{"pmid":"35506437","id":"PMC_35506437","title":"Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A.","date":"2022","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/35506437","citation_count":6,"is_preprint":false},{"pmid":"37247719","id":"PMC_37247719","title":"KLF5-mediated CDCA5 expression promotes tumor development and progression of epithelial ovarian carcinoma.","date":"2023","source":"Experimental cell 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bioinformatics techniques.","date":"2024","source":"BMC gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/38890649","citation_count":4,"is_preprint":false},{"pmid":"40155519","id":"PMC_40155519","title":"Berberine diminishes the malignant progression of non-small cell lung cancer cells by targeting CDCA5 and CCNA2.","date":"2025","source":"Journal of natural medicines","url":"https://pubmed.ncbi.nlm.nih.gov/40155519","citation_count":4,"is_preprint":false},{"pmid":"39214909","id":"PMC_39214909","title":"Therapeutic Potential of PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1 Genes in Triple-Negative Breast Cancer: Correlating Their Expression with Sensitivity to GSK 461364 and IKK 16 Drugs.","date":"2024","source":"Biochemical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39214909","citation_count":4,"is_preprint":false},{"pmid":"35726220","id":"PMC_35726220","title":"Effect of CDCA5 on Proliferation and Metastasis of Triple Negative Breast Cancer Cells under shRNA Interference Technology.","date":"2022","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35726220","citation_count":3,"is_preprint":false},{"pmid":"38539247","id":"PMC_38539247","title":"CDCA5 promoted cell invasion and migration by activating TGF-β1 pathway in human ovarian cancer cells.","date":"2024","source":"Journal of ovarian research","url":"https://pubmed.ncbi.nlm.nih.gov/38539247","citation_count":2,"is_preprint":false},{"pmid":"38658931","id":"PMC_38658931","title":"CDCA5-EEF1A1 interaction promotes progression of clear cell renal cell carcinoma by regulating mTOR signaling.","date":"2024","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/38658931","citation_count":2,"is_preprint":false},{"pmid":"39747150","id":"PMC_39747150","title":"CDC40 suppression induces CDCA5 splicing defects and anti-proliferative effects in lung cancer cells.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39747150","citation_count":1,"is_preprint":false},{"pmid":"37477123","id":"PMC_37477123","title":"[Corrigendum] CDCA5 promotes the progression of prostate cancer by affecting the ERK signalling pathway.","date":"2023","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/37477123","citation_count":1,"is_preprint":false},{"pmid":"38838437","id":"PMC_38838437","title":"The impact of CDCA5 expression on the immune microenvironment and its potential utility as a biomarker for PD-L1/PD-1 inhibitors in lung adenocarcinoma.","date":"2024","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38838437","citation_count":0,"is_preprint":false},{"pmid":"41026320","id":"PMC_41026320","title":"CDCA5 knockdown potentiates olaparib sensitivity in BRCA1-mutated ovarian cancer through autophagy activation.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41026320","citation_count":0,"is_preprint":false},{"pmid":"41699006","id":"PMC_41699006","title":"Dysregulated expression of cell cycle regulators CDC20, PLK1, BUB1, CDC45, CDCA5 in pancreatic ductal adenocarcinoma.","date":"2026","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41699006","citation_count":0,"is_preprint":false},{"pmid":"38550059","id":"PMC_38550059","title":"Retracted: lncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression.","date":"2024","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/38550059","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16636,"output_tokens":2905,"usd":0.046741,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10330,"output_tokens":3856,"usd":0.074025,"stage2_stop_reason":"end_turn"},"total_usd":0.120766,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"CDCA5 transcription is directly driven by E2F1, as demonstrated by luciferase reporter assay and chromatin immunoprecipitation (ChIP) in hepatocellular carcinoma cells.\",\n      \"method\": \"Luciferase reporter assay and chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"Journal of Cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (luciferase reporter + ChIP) in a single lab establishing direct transcriptional regulation\",\n      \"pmids\": [\"31205541\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SPOP (E3 ubiquitin ligase adaptor) interacts with CDCA5 and promotes its polyubiquitin-dependent proteasomal degradation in a degron-dependent manner; prostate cancer-associated SPOP mutations impair this degradation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown rescue experiments\",\n      \"journal\": \"Neoplasia (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus ubiquitination assay plus degron-dependency demonstrated, single lab\",\n      \"pmids\": [\"34509929\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CDCA5 depletion in prostate cancer cells leads to G2/M arrest, severe sister chromatid aggregation disturbance, and apoptosis, confirming its role in sister chromatid cohesion maintenance.\",\n      \"method\": \"shRNA knockdown, flow cytometry, microscopy of sister chromatid phenotypes\",\n      \"journal\": \"Neoplasia (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined cellular phenotype (G2/M arrest and sister chromatid defect), single lab\",\n      \"pmids\": [\"34509929\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TPI1 interacts with CDCA5 (identified by Co-IP and mass spectrometry) and stabilizes CDCA5 protein; TPI1-mediated stabilization of CDCA5 activates the PI3K/AKT/mTOR pathway to promote breast cancer progression.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometric analysis, ubiquitination assay, overexpression/knockdown\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus MS plus ubiquitination assay, single lab\",\n      \"pmids\": [\"35509067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CDCA5 knockdown downregulates PDS5A expression in breast cancer cells, and overexpression of PDS5A reverses the anti-proliferative and anti-migratory effects of CDCA5 inhibition, placing PDS5A downstream of CDCA5.\",\n      \"method\": \"shRNA knockdown, PDS5A overexpression rescue, western blot, proliferation/migration assays\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — rescue epistasis experiment in a single lab with no direct binding assay\",\n      \"pmids\": [\"35506437\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CDCA5 promotes binding of transcription factor E2F1 to the FOXM1 promoter, leading to FOXM1 upregulation and activation of the Wnt/β-catenin signaling pathway in breast cancer cells.\",\n      \"method\": \"Co-IP, ChIP, dual-luciferase reporter assay, FOXM1 knockdown rescue\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — three orthogonal methods (Co-IP, ChIP, luciferase) in single lab\",\n      \"pmids\": [\"38978058\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Transcription factor KLF5 binds to a specific site in the CDCA5 promoter and directly promotes CDCA5 expression in epithelial ovarian cancer cells; KLF5 overexpression rescues the effects of CDCA5 knockdown.\",\n      \"method\": \"ChIP, promoter binding assay, KLF5 overexpression rescue\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ChIP with rescue experiment, single lab, abstract does not detail orthogonal promoter validation\",\n      \"pmids\": [\"37247719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CDCA5 interacts with EEF1A1 (Eukaryotic Translation Elongation Factor 1 Alpha 1), identified by Co-IP and LC-MS/MS, and this interaction regulates mTOR signaling to promote clear cell renal cell carcinoma progression.\",\n      \"method\": \"Co-immunoprecipitation, LC-MS/MS mass spectrometry, knockdown/overexpression\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus MS identification of binding partner, single lab\",\n      \"pmids\": [\"38658931\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CDCA5 promotes invasion and migration of ovarian cancer cells via activation of the TGF-β1/Smad2/3 signaling pathway, as demonstrated by RNA sequencing identifying ECM/TGF pathway enrichment and functional invasion assays.\",\n      \"method\": \"RNA sequencing, functional invasion/migration assays, pathway inhibitor experiments\",\n      \"journal\": \"Journal of ovarian research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptomics-informed pathway placement with functional assays, single lab, no direct protein interaction shown\",\n      \"pmids\": [\"38539247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CDC40 knockdown induces retention of the first intron of CDCA5 pre-mRNA, causing increased unspliced CDCA5 transcript and decreased CDCA5 protein; CDC40 spliceosome interactions were confirmed by protein-protein interaction experiments.\",\n      \"method\": \"siRNA knockdown, global transcriptional/splicing analysis, RT-PCR for intron retention, protein-protein interaction assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct molecular mechanism (intron retention) demonstrated by multiple methods (splicing analysis + protein interaction mapping), single lab\",\n      \"pmids\": [\"39747150\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CDCA5 promotes cell cycle progression in bladder cancer cells by upregulating CDC2 and Cyclin B1, and activating the PI3K/AKT/mTOR pathway; CDCA5 also regulates apoptosis through the mitochondrial pathway.\",\n      \"method\": \"shRNA knockdown, overexpression, western blot for cell cycle proteins and pathway components, flow cytometry\",\n      \"journal\": \"Journal of Cancer\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — western blot pathway readouts without direct interaction or epistasis validation, single lab\",\n      \"pmids\": [\"32201512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CDCA5 knockdown reduces ERK phosphorylation in prostate cancer cells, indicating CDCA5 functions upstream of the ERK signaling pathway to promote proliferation.\",\n      \"method\": \"shRNA knockdown, western blot for phospho-ERK, proliferation assays in vitro and xenograft\",\n      \"journal\": \"Oncology reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — western blot phosphorylation readout, single method for pathway placement, single lab; note corrigendum issued for figure assembly error\",\n      \"pmids\": [\"33650660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CDCA5 interacts with Cyclin A2 (CCNA2) in NSCLC cells, as identified by Co-immunoprecipitation, and modulates CCNA2 expression; berberine treatment reduces both CDCA5 and CCNA2 levels.\",\n      \"method\": \"Co-immunoprecipitation, western blot, overexpression rescue\",\n      \"journal\": \"Journal of natural medicines\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP result, single lab, functional context limited to drug treatment context\",\n      \"pmids\": [\"40155519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CDCA5 knockdown combined with olaparib synergistically suppresses PI3K/AKT/mTOR signaling, activates autophagy, and exacerbates DNA damage in BRCA1-mutated ovarian cancer cells; pharmacological PI3K/AKT/mTOR activation reverses these effects, placing the pathway mechanistically downstream of CDCA5.\",\n      \"method\": \"siRNA knockdown, CCK-8, immunofluorescence, TEM, western blot, PI3K pathway activator rescue, xenograft model\",\n      \"journal\": \"Discover oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — pathway rescue experiment in single lab without direct interaction data\",\n      \"pmids\": [\"41026320\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CDCA5 (sororin) is a regulator of sister chromatid cohesion whose expression is transcriptionally driven by E2F1 (and KLF5 in some contexts), stabilized by TPI1, and targeted for polyubiquitin-dependent proteasomal degradation by the SPOP E3 adaptor; at the molecular level it interacts with EEF1A1 and Cyclin A2, promotes E2F1 binding to the FOXM1 promoter, and modulates CDC2/Cyclin B1 levels and multiple oncogenic kinase cascades (PI3K/AKT/mTOR, ERK, TGF-β1/Smad2/3) to sustain cell cycle progression, suppress apoptosis, and drive cancer cell proliferation and invasion; its pre-mRNA splicing is regulated by the spliceosome component CDC40.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CDCA5 (sororin) is a regulator of sister chromatid cohesion that is essential for orderly cell cycle progression: its depletion causes G2/M arrest, severe sister chromatid aggregation defects, and apoptosis [#2]. Its abundance is controlled at multiple levels — transcriptionally it is a direct target of E2F1 [#0], while at the protein level it is stabilized by TPI1 [#3] and targeted for polyubiquitin-dependent proteasomal degradation by the E3 ubiquitin ligase adaptor SPOP through a degron-dependent mechanism that is impaired by cancer-associated SPOP mutations [#1]. Its production is further gated post-transcriptionally by the spliceosome component CDC40, whose loss causes retention of the first CDCA5 intron and reduced CDCA5 protein [#9]. Beyond cohesion, CDCA5 physically engages EEF1A1 [#7], and acts to promote E2F1 occupancy of the FOXM1 promoter, driving FOXM1 upregulation and Wnt/\\u03b2-catenin activation [#5]. Across cancer contexts these activities converge on sustained proliferation and invasion, with PI3K/AKT/mTOR signaling placed mechanistically downstream of CDCA5 [#3, #13].\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Established how CDCA5 expression is driven in proliferating cancer cells by identifying its upstream transcriptional activator, linking it to the E2F cell-cycle program.\",\n      \"evidence\": \"Luciferase reporter assay and ChIP in hepatocellular carcinoma cells\",\n      \"pmids\": [\"31205541\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not address whether E2F1 regulation holds across other tissues\", \"No measurement of how this transcriptional input couples to cohesion function\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected CDCA5 to cell cycle effectors and survival, showing depletion lowers CDC2/Cyclin B1 and PI3K/AKT/mTOR output while engaging the mitochondrial apoptotic pathway.\",\n      \"evidence\": \"shRNA knockdown/overexpression with western blot and flow cytometry in bladder cancer cells\",\n      \"pmids\": [\"32201512\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Western-blot pathway readouts without direct interaction or epistasis\", \"Does not establish whether PI3K/AKT/mTOR effects are direct or secondary to cell-cycle arrest\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Resolved how CDCA5 protein levels are degraded by identifying SPOP as the E3 adaptor mediating degron-dependent polyubiquitination, and explained how SPOP mutations elevate CDCA5.\",\n      \"evidence\": \"Reciprocal Co-IP, ubiquitination assay, and degron-dependency rescue in prostate cancer cells\",\n      \"pmids\": [\"34509929\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific lysine residues ubiquitinated not mapped\", \"Whether degradation is cell-cycle phase-restricted not addressed\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Confirmed the cohesion-maintenance function of CDCA5 by defining the cellular consequences of its loss, anchoring its sororin identity.\",\n      \"evidence\": \"shRNA knockdown with flow cytometry and microscopy of sister chromatid phenotypes in prostate cancer cells\",\n      \"pmids\": [\"34509929\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular partners at the cohesin complex not characterized in this corpus\", \"Does not distinguish direct cohesion role from indirect cell-cycle arrest\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Placed CDCA5 upstream of ERK signaling, extending its proliferative role beyond the cell-cycle machinery.\",\n      \"evidence\": \"shRNA knockdown with phospho-ERK western blot, proliferation and xenograft assays in prostate cancer\",\n      \"pmids\": [\"33650660\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single phosphorylation readout for pathway placement\", \"Corrigendum issued for figure assembly error\", \"Mechanism linking CDCA5 to ERK undefined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified TPI1 as a CDCA5 binding partner that stabilizes the protein, revealing a positive post-translational input that counterbalances SPOP-mediated turnover.\",\n      \"evidence\": \"Co-IP, mass spectrometry, and ubiquitination assays in breast cancer cells\",\n      \"pmids\": [\"35509067\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether TPI1 directly competes with SPOP not tested\", \"Structural basis of the TPI1\\u2013CDCA5 interaction unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Positioned PDS5A downstream of CDCA5 through epistasis, linking CDCA5 to a cohesion-associated effector in proliferation and migration.\",\n      \"evidence\": \"shRNA knockdown with PDS5A overexpression rescue, western blot and functional assays in breast cancer\",\n      \"pmids\": [\"35506437\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct binding assay between CDCA5 and PDS5A\", \"Single-lab epistasis only\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Added KLF5 as a second transcriptional activator of CDCA5, indicating context-dependent upstream control in ovarian cancer.\",\n      \"evidence\": \"ChIP, promoter binding assay, and KLF5 overexpression rescue in epithelial ovarian cancer cells\",\n      \"pmids\": [\"37247719\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Orthogonal promoter validation not detailed\", \"Relationship to E2F1-driven regulation not reconciled\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined a transcriptional output of CDCA5 by showing it promotes E2F1 binding to the FOXM1 promoter, driving FOXM1 and Wnt/\\u03b2-catenin activation.\",\n      \"evidence\": \"Co-IP, ChIP, dual-luciferase reporter, and FOXM1 knockdown rescue in breast cancer cells\",\n      \"pmids\": [\"38978058\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How a cohesion protein facilitates E2F1 promoter occupancy mechanistically unclear\", \"Direct CDCA5\\u2013E2F1 contact at chromatin not structurally defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified EEF1A1 as a direct CDCA5 partner coupling the protein to mTOR signaling in renal cancer, broadening its interactome beyond the cohesion apparatus.\",\n      \"evidence\": \"Co-IP and LC-MS/MS with knockdown/overexpression in clear cell renal cell carcinoma\",\n      \"pmids\": [\"38658931\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction interface not mapped\", \"Whether EEF1A1 binding is cohesion-independent unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linked CDCA5 to invasion via TGF-\\u03b21/Smad2/3 signaling, extending its role into metastatic phenotypes.\",\n      \"evidence\": \"RNA sequencing, invasion/migration assays, and pathway inhibitor experiments in ovarian cancer\",\n      \"pmids\": [\"38539247\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct protein interaction shown\", \"Pathway placement inferred from transcriptomics\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed post-transcriptional control of CDCA5 by the spliceosome, showing CDC40 loss causes first-intron retention and reduced CDCA5 protein.\",\n      \"evidence\": \"siRNA knockdown, splicing analysis, RT-PCR for intron retention, and protein-protein interaction assays\",\n      \"pmids\": [\"39747150\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether CDC40 directly binds CDCA5 pre-mRNA not shown\", \"Physiological conditions altering this splicing not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified Cyclin A2 as a CDCA5 partner in lung cancer and connected both to berberine sensitivity, reinforcing CDCA5's cell-cycle interactions.\",\n      \"evidence\": \"Co-IP, western blot, and overexpression rescue in NSCLC cells\",\n      \"pmids\": [\"40155519\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation\", \"Functional context limited to drug treatment\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated therapeutic synergy of CDCA5 depletion with olaparib via PI3K/AKT/mTOR suppression, autophagy, and DNA damage, placing the pathway downstream of CDCA5.\",\n      \"evidence\": \"siRNA knockdown, CCK-8, immunofluorescence, TEM, PI3K pathway activator rescue, and xenograft in BRCA1-mutated ovarian cancer\",\n      \"pmids\": [\"41026320\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct interaction data\", \"Mechanism linking CDCA5 to DNA damage repair undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CDCA5's core cohesion function mechanistically connects to the multiple oncogenic signaling cascades (PI3K/AKT/mTOR, ERK, TGF-\\u03b21/Smad, Wnt) attributed to it remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of CDCA5 in any complex within this corpus\", \"Whether signaling roles are direct or downstream of cell-cycle arrest unresolved\", \"Direct cohesin-complex partners not characterized in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SPOP\", \"TPI1\", \"EEF1A1\", \"CCNA2\", \"E2F1\", \"CDC40\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}