{"gene":"JDP2","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":2002,"finding":"JDP2 recruits a histone deacetylase 3 (HDAC3) complex to the differentiation response element (DRE) in the c-jun promoter, thereby inhibiting ATF-2/p300-mediated transactivation and repressing retinoic acid-induced differentiation of F9 cells. ChIP assays showed the JDP2/HDAC3 complex is replaced by the p300 complex upon RA treatment, accompanied by changes in histone acetylation status.","method":"Transient transfection, chromatin immunoprecipitation (ChIP), co-immunoprecipitation, reporter assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal ChIP and co-IP with multiple orthogonal methods (reporter assay, ChIP, co-IP) in a single rigorous study","pmids":["12052888"],"is_preprint":false},{"year":2006,"finding":"JDP2 directly inhibits p300-mediated acetylation of core histones both in vitro and in vivo, requiring the N-terminal 35 residues and the DNA-binding region. JDP2 also exhibits histone-chaperone activity in vitro (nucleosome assembly assay).","method":"In vitro histone acetylation assay, in vivo acetylation assay, nucleosome assembly assay, deletion mutagenesis","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with mutagenesis plus in vivo validation, multiple orthogonal methods in one rigorous study","pmids":["16518400"],"is_preprint":false},{"year":2001,"finding":"JDP2 is phosphorylated by c-Jun N-terminal kinase (JNK) both in vitro and in vivo; the phosphoacceptor site is Thr148, and substitution of Thr148 to Ala blocks JNK-dependent phosphorylation. JDP2 contains a putative JNK docking site.","method":"In vitro kinase assay, in vivo phosphorylation assay, site-directed mutagenesis (T148A)","journal":"FEBS letters","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase assay plus mutagenesis plus in vivo phosphorylation, single lab but multiple orthogonal methods","pmids":["11602244"],"is_preprint":false},{"year":2011,"finding":"Phosphorylation of JDP2 on Thr148 by JNK targets JDP2 for proteasomal degradation. Replacement of Thr148 with Ala stabilizes JDP2 under stimuli that activate JNK (serum, anisomycin, UV, cycloheximide), while T148E (phospho-mimetic) destabilizes it. A JNK inhibitor (SP600125) blocks degradation, whereas p38 and MEK inhibitors do not. The proteasome inhibitor MG132 rescues degradation.","method":"Site-directed mutagenesis, pharmacological inhibitors, cycloheximide chase, proteasome inhibitor rescue, western blot","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — mutagenesis plus multiple pharmacological dissections, single lab but multiple orthogonal approaches","pmids":["21463260"],"is_preprint":false},{"year":2001,"finding":"JDP2 represses p53 transcription via a conserved atypical AP-1 site in the p53 promoter, thereby promoting cell survival following UV irradiation.","method":"Reporter assay, UV irradiation, cell viability assay, overexpression","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assay with functional readout (cell survival), single lab","pmids":["11287607"],"is_preprint":false},{"year":2003,"finding":"JDP2 overexpression activates TRAP and cathepsin K gene promoters in RAW264.7 cells; retroviral expression of JDP2 in mouse primary bone marrow cells facilitates RANKL-induced formation of TRAP-positive multinuclear osteoclasts, and antisense oligonucleotides to JDP2 suppress sRANKL-induced osteoclast formation.","method":"Retroviral overexpression, transient transfection, antisense oligonucleotide knockdown, TRAP staining, promoter reporter assay","journal":"The Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss- and gain-of-function with specific cellular readout, single lab","pmids":["12707301"],"is_preprint":false},{"year":2012,"finding":"In Jdp2−/− mice, osteoclastogenesis is impaired (osteopetrosis phenotype). Jdp2 directly suppresses ATF3 expression via inhibition of histone acetylation at the ATF3 promoter, and this suppression is required for normal neutrophil differentiation and bactericidal function.","method":"Jdp2 knockout mouse, bone histology, neutrophil differentiation assays, ChIP for histone acetylation, gene expression analysis","journal":"Immunity","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo KO with multiple defined phenotypes plus ChIP mechanistic validation, single lab with comprehensive analyses","pmids":["23200825"],"is_preprint":false},{"year":2009,"finding":"JDP2-deficient MEFs exhibit resistance to replicative senescence. In the absence of JDP2, increased H3K27 methylation at the p16Ink4a promoter occurs, and Polycomb repressive complexes (PRC-1 and PRC-2) bind efficiently to repress p16Ink4a. Conversely, JDP2 overexpression induces p16Ink4a and p19Arf expression.","method":"Jdp2 KO MEFs, ChIP for H3K27 methylation and PRC binding, gene expression, overexpression","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP-based mechanistic analysis plus KO and overexpression, multiple orthogonal methods, single lab","pmids":["19233846"],"is_preprint":false},{"year":2010,"finding":"JDP2 is recruited to the AP-1 site in the cyclin-A2 (Ccna2) promoter and represses its transcription. Jdp2 KO MEFs and TPA-treated skin show elevated cyclin-A2 mRNA and increased cell proliferation; reintroduction of JDP2 represses Ccna2 transcription and cell-cycle progression.","method":"Jdp2 KO mice, ChIP at cyclin-A2 promoter, qRT-PCR, colony formation, re-expression rescue","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP plus KO plus rescue experiment, single lab with multiple orthogonal methods","pmids":["20802531"],"is_preprint":false},{"year":2007,"finding":"JDP2 represses adipocyte differentiation by inhibiting histone H3 acetylation at the C/EBPδ gene promoter, thereby suppressing C/EBPδ transcription. Jdp2 KO MEFs show higher susceptibility to adipocyte differentiation and elevated C/EBP family gene expression.","method":"Jdp2 KO mice/MEFs, ChIP for histone H3 acetylation, promoter reporter assay, adipocyte differentiation assay","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP plus KO phenotype plus reporter assay, multiple orthogonal methods, single lab","pmids":["17464331"],"is_preprint":false},{"year":2002,"finding":"Ectopic expression of JDP2 in C2C12 myoblasts inhibits cell-cycle progression and induces spontaneous muscle cell differentiation; JDP2 induces p38 kinase activity in both C2 and RD cells programmed to differentiate.","method":"Ectopic overexpression, cell-cycle analysis, myotube formation assay, p38 kinase activity assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function with specific cellular phenotype and p38 kinase activity measurement, single lab","pmids":["12171923"],"is_preprint":false},{"year":2009,"finding":"JDP2 suppresses ATF3 transcription by binding to both a consensus ATF/CRE site and a non-consensus ATF3 auto-repression element in the ATF3 promoter. JDP2 KO MEFs display elevated ATF3 protein and potentiated ATF3 induction in response to serum or ER stress; JDP2 overexpressing mice show attenuated ATF3 induction.","method":"JDP2 KO MEFs, JDP2 overexpression transgenic mice, promoter reporter assay, western blot, serum/ER stress stimulation","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO and transgenic OE with promoter reporter assay, replicated in vivo and in vitro","pmids":["19233874"],"is_preprint":false},{"year":2008,"finding":"JDP2 forms a heterodimer with CHOP10 (C/EBP homologous protein) via leucine zipper motifs; the basic domain of CHOP10 contributes to DNA binding. This JDP2-CHOP10 complex strongly activates transcription from TPA-response element (TRE)-containing promoters but not CRE-containing promoters, both in vitro and in vivo (EMSA and ChIP). JDP2 overexpression increases cell viability after ER stress and counteracts CHOP10 pro-apoptotic activity.","method":"Co-immunoprecipitation, EMSA, ChIP, reporter assay, cell viability assay","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP plus EMSA plus ChIP plus functional reporter, multiple orthogonal methods, single lab","pmids":["18463134"],"is_preprint":false},{"year":2009,"finding":"JDP2 interacts with the progesterone receptor (PR) through its bZIP domain; NMR chemical shift mapping shows that JDP2 binding residues reside predominantly within the carboxyl-terminal extension (CTE) of the PR DNA-binding domain. Point mutations and CTE domain swap experiments confirm that JDP2-CTE interaction is functionally required for enhancement of PR transcriptional activity.","method":"NMR chemical shift mapping, peptide competition, site-directed mutagenesis, CTE domain swap, transcriptional reporter assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR structural mapping plus mutagenesis plus functional reporter, multiple orthogonal methods in one rigorous study","pmids":["19553667"],"is_preprint":false},{"year":2011,"finding":"JDP2 binds the ZII cis-element (an ATF/CRE/AP-1 binding site) in the Epstein-Barr virus BZLF1 promoter (Zp), and this binding correlates with HDAC3 association and reduced histone acetylation at Zp. Silencing of endogenous JDP2 by RNAi increases viral early gene products and viral DNA replication, indicating JDP2 maintains EBV latency.","method":"Reporter assay, EMSA, ChIP, mutant virus analysis, RNAi knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — EMSA, ChIP, and functional RNAi with viral replication readout, multiple orthogonal methods","pmids":["21525011"],"is_preprint":false},{"year":2008,"finding":"IRF2-BP1 (IRF2-binding protein-1) was identified as a JDP2-binding protein and acts as a JDP2 ubiquitin ligase via its RING-finger domain, enhancing polyubiquitination of JDP2. IRF2-BP1 also represses ATF2-mediated transcriptional activation from a CRE-containing promoter.","method":"Epitope-tagging pulldown, polyubiquitination assay, reporter assay","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single pulldown plus ubiquitination assay, single lab, single study","pmids":["18671972"],"is_preprint":false},{"year":2008,"finding":"JDP2 acts as a repressor of CHOP transcription by binding to the amino acid response element (AARE) in the CHOP promoter in unstimulated cells; its binding decreases following amino acid starvation. JDP2 is functionally associated with HDAC3 to inhibit CHOP transcription.","method":"EMSA, ChIP, reporter assay, amino acid starvation","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — EMSA plus ChIP plus reporter assay, single lab","pmids":["18396163"],"is_preprint":false},{"year":2012,"finding":"JDP2 transcriptionally represses the Trp53 promoter via an atypical AP-1 site; JDP2 expression negatively regulates Trp53 expression levels in a leukaemogenesis context.","method":"Transposon insertional mutagenesis screen, promoter reporter assay, gene expression analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assay plus in vivo genetic screen, single lab","pmids":["22370638"],"is_preprint":false},{"year":2018,"finding":"JDP2 directly regulates MCL1 transcription; depletion of JDP2 by shRNA knockdown leads to apoptosis in T-ALL cells. JDP2-overexpressing zebrafish thymocytes express high levels of mcl1 and demonstrate steroid resistance in vivo.","method":"shRNA knockdown, transcriptional reporter/ChIP (implied by 'direct transcriptional regulation'), transgenic zebrafish model, gene expression analysis","journal":"The Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — shRNA KD with apoptosis readout plus in vivo transgenic model, single lab","pmids":["29941549"],"is_preprint":false},{"year":2019,"finding":"Upon genotoxic stress, ATM phosphorylates JDP2, enabling formation of a β-catenin/JDP2/PRMT5 chromatin complex. This complex recruits WDR5/MLL methyltransferase complexes, producing H3R2me1/H3R2me2s and H3K4 methylation at promoters of GSH-metabolic cascade genes, reestablishing glutathione homeostasis and reducing ROS.","method":"Co-immunoprecipitation, ChIP, histone modification assays, pharmacological inhibition (OICR-9429), genotoxic stress treatment","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus ChIP plus histone modification assays plus pharmacological rescue, multiple orthogonal methods in one study","pmids":["31434880"],"is_preprint":false},{"year":2016,"finding":"JDP2 acts as a repressor of FSHβ (Fshb) transcription by occupying the AP-1-binding site in the Fshb promoter in a complex with c-JUN. GNRH treatment induces c-FOS to replace JDP2 as c-JUN's binding partner, forming transcriptionally active AP-1; rapid c-FOS degradation then allows reformation of the repressive JDP2 complex. Jdp2 null female mice show elevated FSH, early puberty, and early reproductive senescence.","method":"ChIP, co-immunoprecipitation, reporter assay, Jdp2 KO mouse reproductive phenotype analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP plus co-IP plus KO phenotype plus reporter assay, multiple orthogonal methods","pmids":["28007961"],"is_preprint":false},{"year":2014,"finding":"Zebrafish doublecortin-like protein kinase (DCLK) C-terminal kinase domain binds JDP2 (identified by two-hybrid screening) and efficiently phosphorylates JDP2 in the presence of histone.","method":"Yeast two-hybrid screening, in vitro kinase assay with histone","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single two-hybrid identification plus single in vitro assay, zebrafish kinase fragment, not confirmed in mammalian system","pmids":["24582561"],"is_preprint":false},{"year":2019,"finding":"ATF3 and JDP2 double-deficient cancer-associated fibroblasts secrete elevated levels of SDF-1 (CXCL12), promoting tumor growth and vascular perfusion. ATF3 and JDP2 regulate SDF-1 transcription and secretion in fibroblasts, and this is potentiated in the presence of cancer cells. SDF-1 depletion in dKO fibroblasts dampened tumor growth.","method":"Double KO mouse, tumor implantation, ELISA, conditioned medium assay, SDF-1 depletion rescue","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo dKO with rescue experiment plus SDF-1 secretion assay, single lab","pmids":["30670778"],"is_preprint":false},{"year":2020,"finding":"In Jdp2 KO cerebellar granule cell progenitors (GCPs), p21Cip1 and Nrf2 form a complex that binds antioxidant response elements in the Slc7a11 promoter, increasing Slc7a11 (xCT cystine-glutamate exchanger) expression and glutathione levels, thus reducing ROS and conferring resistance to ROS-mediated apoptosis.","method":"Jdp2 KO mice, primary GCP cultures, ChIP, co-immunoprecipitation, ROS measurement, apoptosis assay","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus co-IP plus KO phenotype, single lab","pmids":["32188872"],"is_preprint":false},{"year":2021,"finding":"JDP2 forms an activation complex with AHR-ARNT and NRF2-sMAF at dioxin response elements (DRE) and antioxidant response elements (ARE) in the AHR promoter in response to DMSO, regulating AHR promoter activity and ROS production. Jdp2 is required for AHR promoter activation; co-immunoprecipitation and ChIP confirmed JDP2 presence in the complex at DRE sites.","method":"Co-immunoprecipitation, ChIP, promoter reporter assay, Jdp2 KO MEFs, DMSO treatment","journal":"Cell biology and toxicology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus ChIP plus KO, single lab, multiple methods","pmids":["33723743"],"is_preprint":false},{"year":2020,"finding":"JDP2 is directly regulated at the transcriptional level by ATF4; JDP2 knockdown enhances expression of ATF4 target genes including ASNS, DR4, and DR5. JDP2 overexpression represses ER stress-mediated DR5 promoter activation (transient reporter assay). JDP2 knockdown increases TRAIL sensitivity in HeLa cells, indicating JDP2 functions as a negative feedback regulator of the ATF4 pathway to confer TRAIL resistance.","method":"siRNA knockdown, reporter assay, western blot, TRAIL sensitivity assay","journal":"FEBS open bio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA KD plus reporter assay plus functional TRAIL assay, single lab","pmids":["33108704"],"is_preprint":false},{"year":2024,"finding":"JDP2 directly interacts with p53 via its C-terminal domain (confirmed by co-IP and domain mapping). JDP2 enhances p53 transactivation in p53-null H1299 cells reconstituted with WT p53 but fails to enhance transactivation of hotspot mutant p53. JDP2 reduces MDM2 levels to enhance p53 transactivation, and slightly stabilizes p53 in CHX chase experiments.","method":"Co-immunoprecipitation, domain deletion analysis, reporter assay (p53 14X RE-Luc), CHX chase, western blot","journal":"Cancers","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus reporter assay plus CHX chase, multiple orthogonal methods, single lab","pmids":["38473360"],"is_preprint":false},{"year":2014,"finding":"p53 significantly represses the transcriptional activity of the JDP2 promoter, suggesting a negative feedback loop between JDP2 (which represses p53) and p53 (which represses JDP2).","method":"Promoter cloning, reporter assay, primer extension analysis","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reporter assay with promoter mapping, single lab, single method","pmids":["25026555"],"is_preprint":false},{"year":2022,"finding":"JDP2 transcriptionally suppresses ITGBL1 promoter activity (dual-luciferase assay); ITGBL1 overexpression reverses the effects of JDP2 upregulation on pancreatic cancer cell proliferation, migration, and invasion.","method":"Dual-luciferase reporter assay, gain/loss-of-function, cell proliferation and invasion assays","journal":"Brazilian journal of medical and biological research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single reporter assay plus overexpression rescue, single lab","pmids":["35584452"],"is_preprint":false},{"year":2022,"finding":"JDP2 directly activates PDE4B transcription in cardiomyocytes (confirmed by dual-luciferase reporter and ChIP assays); JDP2 overexpression upregulates PDE4B expression and exacerbates hypoxia/reoxygenation-induced H9c2 cell injury.","method":"Dual-luciferase reporter assay, ChIP, overexpression, hypoxia/reoxygenation model","journal":"Experimental and therapeutic medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — ChIP plus reporter assay, single lab","pmids":["35401806"],"is_preprint":false},{"year":2024,"finding":"IRF2BP2 interacts with the AP-1 heterodimer ATF7/JDP2, is recruited to chromatin by ATF7/JDP2, and counteracts its gene-activating function in AML cells. Loss of IRF2BP2 leads to overactivation of inflammatory pathways driven by ATF7/JDP2.","method":"Co-immunoprecipitation, ChIP-seq, loss-of-function (IRF2BP2 KO), gene expression analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus ChIP plus KO with transcriptome readout, single lab","pmids":["38801077"],"is_preprint":false},{"year":2019,"finding":"A combination of Jdp2 with six other factors (Jhdm1b, Mkk6, Glis1, Nanog, Essrb, Sall4) can reprogram mouse embryonic fibroblasts to chimera-competent iPSCs. ATAC-seq and RNA-seq reveal that Jdp2 participates in dynamically closing and opening chromatin loci as part of a cooperative reprogramming process.","method":"Reprogramming assay, RNA-seq, ATAC-seq, chimera injection, dropout experiments","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional reprogramming with ATAC-seq chromatin analysis, single lab","pmids":["31216469"],"is_preprint":false},{"year":2017,"finding":"CGRP suppresses β-glucan-induced inflammation and osteoclast multinucleation via direct suppression of NF-κB p65 by the transcriptional repressor Jdp2.","method":"In vivo nociceptor ablation, TRPV1/TRPA1 knockout, CGRP treatment, inflammatory readout, mechanistic pathway dissection","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo genetic KO with pathway dissection, single lab","pmids":["28658621"],"is_preprint":false}],"current_model":"JDP2 is a bZIP transcriptional repressor (and context-dependent activator) of AP-1 target genes that acts through multiple chromatin-level mechanisms: it recruits HDAC3 to promoters to repress histone acetylation, directly inhibits p300-mediated histone acetylation via an N-terminal INHAT domain, and exhibits histone-chaperone activity; it is phosphorylated on Thr148 by JNK, which targets it for proteasomal degradation; it forms functional heterodimers with Jun/ATF2, CHOP10, and ATF7, and interacts with partners including p53, progesterone receptor (via the CTE), and IRF2BP1 (a JDP2 ubiquitin ligase); and it controls diverse biological programs including osteoclastogenesis, neutrophil differentiation, adipogenesis, myogenesis, cellular senescence (via epigenetic regulation of p16Ink4a/Arf through Polycomb complexes), cell-cycle progression (via Cyclin-A2 repression), FSHβ transcription, EBV latency, and redox homeostasis (via the β-catenin/JDP2/PRMT5 complex and the AHR-NRF2-JDP2 axis)."},"narrative":{"mechanistic_narrative":"JDP2 is a bZIP transcription factor that binds AP-1/ATF-CRE cis-elements and acts predominantly as a transcriptional repressor through chromatin-level mechanisms, thereby controlling differentiation, proliferation, stress responses, and redox homeostasis across multiple lineages [PMID:12052888, PMID:23200825, PMID:20802531]. It represses target promoters by recruiting an HDAC3 complex and by directly inhibiting p300-mediated acetylation of core histones through its N-terminal region and DNA-binding domain, activities complemented by intrinsic histone-chaperone (nucleosome-assembly) activity [PMID:12052888, PMID:16518400]. Through these mechanisms JDP2 suppresses c-jun, ATF3, cyclin-A2, C/EBPδ, and CHOP transcription, and silences higher-order chromatin states such as Polycomb-mediated repression of the p16Ink4a/p19Arf locus, with corresponding control of retinoic-acid differentiation, osteoclastogenesis and neutrophil differentiation, adipogenesis, cell-cycle progression, and replicative senescence [PMID:12052888, PMID:23200825, PMID:19233846, PMID:20802531, PMID:17464331, PMID:18396163]. JDP2 activity is gated by JNK, which phosphorylates Thr148 to target the protein for proteasomal degradation, and by the RING-finger ubiquitin ligase IRF2BP1 [PMID:11602244, PMID:21463260, PMID:18671972]. Its DNA-binding specificity and transcriptional output are tuned by partner exchange: it heterodimerizes with c-JUN, ATF7, CHOP10, and ATF2, and interacts with the progesterone receptor, p53, and chromatin-modifying complexes [PMID:18463134, PMID:19553667, PMID:28007961, PMID:38473360, PMID:38801077]. JDP2 also functions in genotoxic and oxidative stress: ATM-phosphorylated JDP2 nucleates a β-catenin/JDP2/PRMT5 complex that recruits WDR5/MLL to install activating histone methylation at glutathione-metabolic genes, restoring redox balance [PMID:31434880]. In disease contexts it represses Trp53 and activates MCL1 to promote leukemic survival and steroid resistance [PMID:22370638, PMID:29941549].","teleology":[{"year":2001,"claim":"Establishing how JDP2 is regulated post-translationally, JNK was shown to directly phosphorylate JDP2 at a defined residue, placing it downstream of stress kinase signaling.","evidence":"In vitro and in vivo kinase assays with T148A mutagenesis","pmids":["11602244"],"confidence":"High","gaps":["Functional consequence of Thr148 phosphorylation not resolved here","Identity of the relevant JNK isoform not defined"]},{"year":2001,"claim":"JDP2 was placed in the survival pathway by showing it represses the p53 promoter through an atypical AP-1 site, defining an early transcriptional-repressor function.","evidence":"Reporter assay and UV-induced cell viability with overexpression","pmids":["11287607"],"confidence":"Medium","gaps":["No direct DNA-binding/occupancy confirmation at the endogenous promoter","Physiological relevance beyond UV challenge unclear"]},{"year":2002,"claim":"The core repression mechanism was defined: JDP2 recruits HDAC3 to a target promoter and is displaced by p300 upon differentiation cues, linking JDP2 to dynamic histone acetylation control.","evidence":"ChIP, co-IP, and reporter assays in RA-treated F9 cells","pmids":["12052888"],"confidence":"High","gaps":["Direct biochemical interaction surface with HDAC3 not mapped","Generality across other promoters not yet shown"]},{"year":2006,"claim":"JDP2 was shown to act intrinsically on chromatin — directly inhibiting p300 acetyltransferase activity and assembling nucleosomes — establishing it as a bona fide chromatin regulator, not merely a DNA-binding adaptor.","evidence":"In vitro/in vivo acetylation assays, nucleosome assembly assay, deletion mutagenesis","pmids":["16518400"],"confidence":"High","gaps":["Structural basis of INHAT-like inhibition not solved","Relative in vivo contribution of HDAC recruitment vs direct p300 inhibition unquantified"]},{"year":2007,"claim":"Linking the chromatin mechanism to a developmental program, JDP2 was shown to restrain adipogenesis by deacetylating the C/EBPδ promoter.","evidence":"Jdp2 KO MEFs, ChIP for H3 acetylation, adipocyte differentiation and reporter assays","pmids":["17464331"],"confidence":"High","gaps":["Upstream signals controlling JDP2 at this locus not defined"]},{"year":2008,"claim":"Partner-dependent functional switching was demonstrated: heterodimerization with CHOP10 converts JDP2 into a TRE-selective activator that opposes CHOP10-driven apoptosis under ER stress.","evidence":"Co-IP, EMSA, ChIP, reporter and viability assays","pmids":["18463134"],"confidence":"High","gaps":["In vivo relevance of the JDP2-CHOP10 complex not tested","Determinants of TRE vs CRE selectivity incompletely defined"]},{"year":2008,"claim":"A degradation route was added by identifying IRF2BP1 as a RING-finger ubiquitin ligase for JDP2, defining a JNK-independent control of JDP2 levels.","evidence":"Tagged pulldown, polyubiquitination and reporter assays","pmids":["18671972"],"confidence":"Medium","gaps":["Single pulldown without reciprocal validation","Endogenous regulation and physiological context unaddressed"]},{"year":2009,"claim":"JDP2 was connected to senescence control, showing its absence permits Polycomb (PRC1/PRC2) repression of p16Ink4a, defining an epigenetic gatekeeper role.","evidence":"Jdp2 KO MEFs, ChIP for H3K27me and PRC binding, overexpression","pmids":["19233846"],"confidence":"High","gaps":["Mechanism by which JDP2 antagonizes PRC recruitment unresolved"]},{"year":2009,"claim":"Direct promoter occupancy at consensus and non-consensus sites was demonstrated for ATF3 repression, and structural mapping defined how JDP2 engages the progesterone receptor CTE to modulate its activity.","evidence":"KO/transgenic mice with reporter assays (ATF3); NMR chemical-shift mapping and CTE swaps (PR)","pmids":["19233874","19553667"],"confidence":"High","gaps":["Whether PR enhancement uses the same chromatin machinery as repression unknown"]},{"year":2010,"claim":"A proliferation-control axis was established by showing JDP2 occupies and represses the cyclin-A2 promoter in vivo, restraining cell-cycle progression.","evidence":"Jdp2 KO mice, ChIP, qRT-PCR, rescue re-expression","pmids":["20802531"],"confidence":"High","gaps":["Coordination with other cell-cycle targets not mapped"]},{"year":2011,"claim":"The fate of Thr148 phosphorylation was resolved: it targets JDP2 for proteasomal degradation, coupling stress-kinase signaling to JDP2 turnover.","evidence":"Phospho-mimetic/non-phosphorylatable mutants, kinase/proteasome inhibitors, CHX chase","pmids":["21463260"],"confidence":"High","gaps":["The ubiquitin ligase acting on phospho-JDP2 not identified in this study"]},{"year":2011,"claim":"JDP2 was shown to maintain viral latency, binding the EBV BZLF1 promoter with HDAC3 to suppress lytic reactivation.","evidence":"EMSA, ChIP, RNAi, mutant virus analysis","pmids":["21525011"],"confidence":"High","gaps":["Host signals that relieve JDP2 repression during reactivation undefined"]},{"year":2012,"claim":"In vivo KO confirmed JDP2's developmental roles, showing osteopetrosis from impaired osteoclastogenesis and defective neutrophil differentiation via histone-acetylation-dependent ATF3 suppression.","evidence":"Jdp2 KO mice, bone histology, neutrophil assays, ChIP","pmids":["23200825"],"confidence":"High","gaps":["Cell-autonomous vs niche contributions to bone phenotype not fully separated"]},{"year":2019,"claim":"A genotoxic-stress redox function was defined: ATM-phosphorylated JDP2 nucleates a β-catenin/PRMT5 complex recruiting WDR5/MLL to activate glutathione-metabolic genes, showing JDP2 can also drive activating histone methylation.","evidence":"Co-IP, ChIP, histone-modification assays, WDR5 inhibitor (OICR-9429)","pmids":["31434880"],"confidence":"High","gaps":["ATM phosphosite on JDP2 not mapped","Switch between repressive and activating modes mechanistically unresolved"]},{"year":2018,"claim":"An oncogenic survival role was established in T-ALL, where JDP2 activates MCL1 to confer apoptosis resistance and steroid resistance.","evidence":"shRNA knockdown, transgenic zebrafish, gene expression","pmids":["29941549"],"confidence":"Medium","gaps":["Direct promoter occupancy at MCL1 not fully demonstrated","Cofactor dependence in leukemic cells unknown"]},{"year":2024,"claim":"Refining the JDP2-p53 relationship, JDP2 was shown to bind p53 via its C-terminus, lower MDM2, and enhance WT (but not mutant) p53 transactivation, indicating context-dependent activation rather than uniform repression.","evidence":"Co-IP, domain mapping, p53 reporter, CHX chase","pmids":["38473360"],"confidence":"Medium","gaps":["Reconciliation with earlier Trp53-promoter repression unresolved","Mechanism of MDM2 reduction undefined"]},{"year":2024,"claim":"Partner-specific corepression was mapped in AML, where IRF2BP2 is recruited by the ATF7/JDP2 heterodimer to chromatin and restrains its inflammatory gene-activating output.","evidence":"Co-IP, ChIP-seq, IRF2BP2 KO with transcriptomics","pmids":["38801077"],"confidence":"Medium","gaps":["Whether ATF7/JDP2 activates or represses depends on cofactor balance not fully defined"]},{"year":null,"claim":"How JDP2 toggles between repressive (HDAC3/p300-inhibition) and activating (PRMT5/WDR5/MLL, CHOP10, p53) chromatin outputs at a given locus — and how this is set by partner identity, post-translational modification, and stress state — remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking dimer partner to activation vs repression","No structural model of the JDP2 chromatin-modifying complexes","Phosphosites beyond Thr148 and their ligases incompletely defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,6,8,11,12,20]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[1,11,12,16,20]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[1]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[1]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,8,19]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[7,19]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,6,8,11]},{"term_id":"R-HSA-4839726","term_label":"Chromatin 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complex to the differentiation response element (DRE) in the c-jun promoter, thereby inhibiting ATF-2/p300-mediated transactivation and repressing retinoic acid-induced differentiation of F9 cells. ChIP assays showed the JDP2/HDAC3 complex is replaced by the p300 complex upon RA treatment, accompanied by changes in histone acetylation status.\",\n      \"method\": \"Transient transfection, chromatin immunoprecipitation (ChIP), co-immunoprecipitation, reporter assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal ChIP and co-IP with multiple orthogonal methods (reporter assay, ChIP, co-IP) in a single rigorous study\",\n      \"pmids\": [\"12052888\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"JDP2 directly inhibits p300-mediated acetylation of core histones both in vitro and in vivo, requiring the N-terminal 35 residues and the DNA-binding region. JDP2 also exhibits histone-chaperone activity in vitro (nucleosome assembly assay).\",\n      \"method\": \"In vitro histone acetylation assay, in vivo acetylation assay, nucleosome assembly assay, deletion mutagenesis\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with mutagenesis plus in vivo validation, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"16518400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"JDP2 is phosphorylated by c-Jun N-terminal kinase (JNK) both in vitro and in vivo; the phosphoacceptor site is Thr148, and substitution of Thr148 to Ala blocks JNK-dependent phosphorylation. JDP2 contains a putative JNK docking site.\",\n      \"method\": \"In vitro kinase assay, in vivo phosphorylation assay, site-directed mutagenesis (T148A)\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase assay plus mutagenesis plus in vivo phosphorylation, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"11602244\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Phosphorylation of JDP2 on Thr148 by JNK targets JDP2 for proteasomal degradation. Replacement of Thr148 with Ala stabilizes JDP2 under stimuli that activate JNK (serum, anisomycin, UV, cycloheximide), while T148E (phospho-mimetic) destabilizes it. A JNK inhibitor (SP600125) blocks degradation, whereas p38 and MEK inhibitors do not. The proteasome inhibitor MG132 rescues degradation.\",\n      \"method\": \"Site-directed mutagenesis, pharmacological inhibitors, cycloheximide chase, proteasome inhibitor rescue, western blot\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — mutagenesis plus multiple pharmacological dissections, single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"21463260\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"JDP2 represses p53 transcription via a conserved atypical AP-1 site in the p53 promoter, thereby promoting cell survival following UV irradiation.\",\n      \"method\": \"Reporter assay, UV irradiation, cell viability assay, overexpression\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assay with functional readout (cell survival), single lab\",\n      \"pmids\": [\"11287607\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"JDP2 overexpression activates TRAP and cathepsin K gene promoters in RAW264.7 cells; retroviral expression of JDP2 in mouse primary bone marrow cells facilitates RANKL-induced formation of TRAP-positive multinuclear osteoclasts, and antisense oligonucleotides to JDP2 suppress sRANKL-induced osteoclast formation.\",\n      \"method\": \"Retroviral overexpression, transient transfection, antisense oligonucleotide knockdown, TRAP staining, promoter reporter assay\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss- and gain-of-function with specific cellular readout, single lab\",\n      \"pmids\": [\"12707301\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"In Jdp2−/− mice, osteoclastogenesis is impaired (osteopetrosis phenotype). Jdp2 directly suppresses ATF3 expression via inhibition of histone acetylation at the ATF3 promoter, and this suppression is required for normal neutrophil differentiation and bactericidal function.\",\n      \"method\": \"Jdp2 knockout mouse, bone histology, neutrophil differentiation assays, ChIP for histone acetylation, gene expression analysis\",\n      \"journal\": \"Immunity\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo KO with multiple defined phenotypes plus ChIP mechanistic validation, single lab with comprehensive analyses\",\n      \"pmids\": [\"23200825\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"JDP2-deficient MEFs exhibit resistance to replicative senescence. In the absence of JDP2, increased H3K27 methylation at the p16Ink4a promoter occurs, and Polycomb repressive complexes (PRC-1 and PRC-2) bind efficiently to repress p16Ink4a. Conversely, JDP2 overexpression induces p16Ink4a and p19Arf expression.\",\n      \"method\": \"Jdp2 KO MEFs, ChIP for H3K27 methylation and PRC binding, gene expression, overexpression\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-based mechanistic analysis plus KO and overexpression, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"19233846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"JDP2 is recruited to the AP-1 site in the cyclin-A2 (Ccna2) promoter and represses its transcription. Jdp2 KO MEFs and TPA-treated skin show elevated cyclin-A2 mRNA and increased cell proliferation; reintroduction of JDP2 represses Ccna2 transcription and cell-cycle progression.\",\n      \"method\": \"Jdp2 KO mice, ChIP at cyclin-A2 promoter, qRT-PCR, colony formation, re-expression rescue\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus KO plus rescue experiment, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"20802531\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"JDP2 represses adipocyte differentiation by inhibiting histone H3 acetylation at the C/EBPδ gene promoter, thereby suppressing C/EBPδ transcription. Jdp2 KO MEFs show higher susceptibility to adipocyte differentiation and elevated C/EBP family gene expression.\",\n      \"method\": \"Jdp2 KO mice/MEFs, ChIP for histone H3 acetylation, promoter reporter assay, adipocyte differentiation assay\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus KO phenotype plus reporter assay, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"17464331\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Ectopic expression of JDP2 in C2C12 myoblasts inhibits cell-cycle progression and induces spontaneous muscle cell differentiation; JDP2 induces p38 kinase activity in both C2 and RD cells programmed to differentiate.\",\n      \"method\": \"Ectopic overexpression, cell-cycle analysis, myotube formation assay, p38 kinase activity assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function with specific cellular phenotype and p38 kinase activity measurement, single lab\",\n      \"pmids\": [\"12171923\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"JDP2 suppresses ATF3 transcription by binding to both a consensus ATF/CRE site and a non-consensus ATF3 auto-repression element in the ATF3 promoter. JDP2 KO MEFs display elevated ATF3 protein and potentiated ATF3 induction in response to serum or ER stress; JDP2 overexpressing mice show attenuated ATF3 induction.\",\n      \"method\": \"JDP2 KO MEFs, JDP2 overexpression transgenic mice, promoter reporter assay, western blot, serum/ER stress stimulation\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO and transgenic OE with promoter reporter assay, replicated in vivo and in vitro\",\n      \"pmids\": [\"19233874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"JDP2 forms a heterodimer with CHOP10 (C/EBP homologous protein) via leucine zipper motifs; the basic domain of CHOP10 contributes to DNA binding. This JDP2-CHOP10 complex strongly activates transcription from TPA-response element (TRE)-containing promoters but not CRE-containing promoters, both in vitro and in vivo (EMSA and ChIP). JDP2 overexpression increases cell viability after ER stress and counteracts CHOP10 pro-apoptotic activity.\",\n      \"method\": \"Co-immunoprecipitation, EMSA, ChIP, reporter assay, cell viability assay\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP plus EMSA plus ChIP plus functional reporter, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"18463134\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"JDP2 interacts with the progesterone receptor (PR) through its bZIP domain; NMR chemical shift mapping shows that JDP2 binding residues reside predominantly within the carboxyl-terminal extension (CTE) of the PR DNA-binding domain. Point mutations and CTE domain swap experiments confirm that JDP2-CTE interaction is functionally required for enhancement of PR transcriptional activity.\",\n      \"method\": \"NMR chemical shift mapping, peptide competition, site-directed mutagenesis, CTE domain swap, transcriptional reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR structural mapping plus mutagenesis plus functional reporter, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"19553667\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"JDP2 binds the ZII cis-element (an ATF/CRE/AP-1 binding site) in the Epstein-Barr virus BZLF1 promoter (Zp), and this binding correlates with HDAC3 association and reduced histone acetylation at Zp. Silencing of endogenous JDP2 by RNAi increases viral early gene products and viral DNA replication, indicating JDP2 maintains EBV latency.\",\n      \"method\": \"Reporter assay, EMSA, ChIP, mutant virus analysis, RNAi knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — EMSA, ChIP, and functional RNAi with viral replication readout, multiple orthogonal methods\",\n      \"pmids\": [\"21525011\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"IRF2-BP1 (IRF2-binding protein-1) was identified as a JDP2-binding protein and acts as a JDP2 ubiquitin ligase via its RING-finger domain, enhancing polyubiquitination of JDP2. IRF2-BP1 also represses ATF2-mediated transcriptional activation from a CRE-containing promoter.\",\n      \"method\": \"Epitope-tagging pulldown, polyubiquitination assay, reporter assay\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single pulldown plus ubiquitination assay, single lab, single study\",\n      \"pmids\": [\"18671972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"JDP2 acts as a repressor of CHOP transcription by binding to the amino acid response element (AARE) in the CHOP promoter in unstimulated cells; its binding decreases following amino acid starvation. JDP2 is functionally associated with HDAC3 to inhibit CHOP transcription.\",\n      \"method\": \"EMSA, ChIP, reporter assay, amino acid starvation\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — EMSA plus ChIP plus reporter assay, single lab\",\n      \"pmids\": [\"18396163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"JDP2 transcriptionally represses the Trp53 promoter via an atypical AP-1 site; JDP2 expression negatively regulates Trp53 expression levels in a leukaemogenesis context.\",\n      \"method\": \"Transposon insertional mutagenesis screen, promoter reporter assay, gene expression analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assay plus in vivo genetic screen, single lab\",\n      \"pmids\": [\"22370638\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"JDP2 directly regulates MCL1 transcription; depletion of JDP2 by shRNA knockdown leads to apoptosis in T-ALL cells. JDP2-overexpressing zebrafish thymocytes express high levels of mcl1 and demonstrate steroid resistance in vivo.\",\n      \"method\": \"shRNA knockdown, transcriptional reporter/ChIP (implied by 'direct transcriptional regulation'), transgenic zebrafish model, gene expression analysis\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — shRNA KD with apoptosis readout plus in vivo transgenic model, single lab\",\n      \"pmids\": [\"29941549\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Upon genotoxic stress, ATM phosphorylates JDP2, enabling formation of a β-catenin/JDP2/PRMT5 chromatin complex. This complex recruits WDR5/MLL methyltransferase complexes, producing H3R2me1/H3R2me2s and H3K4 methylation at promoters of GSH-metabolic cascade genes, reestablishing glutathione homeostasis and reducing ROS.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, histone modification assays, pharmacological inhibition (OICR-9429), genotoxic stress treatment\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus ChIP plus histone modification assays plus pharmacological rescue, multiple orthogonal methods in one study\",\n      \"pmids\": [\"31434880\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"JDP2 acts as a repressor of FSHβ (Fshb) transcription by occupying the AP-1-binding site in the Fshb promoter in a complex with c-JUN. GNRH treatment induces c-FOS to replace JDP2 as c-JUN's binding partner, forming transcriptionally active AP-1; rapid c-FOS degradation then allows reformation of the repressive JDP2 complex. Jdp2 null female mice show elevated FSH, early puberty, and early reproductive senescence.\",\n      \"method\": \"ChIP, co-immunoprecipitation, reporter assay, Jdp2 KO mouse reproductive phenotype analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus co-IP plus KO phenotype plus reporter assay, multiple orthogonal methods\",\n      \"pmids\": [\"28007961\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Zebrafish doublecortin-like protein kinase (DCLK) C-terminal kinase domain binds JDP2 (identified by two-hybrid screening) and efficiently phosphorylates JDP2 in the presence of histone.\",\n      \"method\": \"Yeast two-hybrid screening, in vitro kinase assay with histone\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single two-hybrid identification plus single in vitro assay, zebrafish kinase fragment, not confirmed in mammalian system\",\n      \"pmids\": [\"24582561\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ATF3 and JDP2 double-deficient cancer-associated fibroblasts secrete elevated levels of SDF-1 (CXCL12), promoting tumor growth and vascular perfusion. ATF3 and JDP2 regulate SDF-1 transcription and secretion in fibroblasts, and this is potentiated in the presence of cancer cells. SDF-1 depletion in dKO fibroblasts dampened tumor growth.\",\n      \"method\": \"Double KO mouse, tumor implantation, ELISA, conditioned medium assay, SDF-1 depletion rescue\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo dKO with rescue experiment plus SDF-1 secretion assay, single lab\",\n      \"pmids\": [\"30670778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In Jdp2 KO cerebellar granule cell progenitors (GCPs), p21Cip1 and Nrf2 form a complex that binds antioxidant response elements in the Slc7a11 promoter, increasing Slc7a11 (xCT cystine-glutamate exchanger) expression and glutathione levels, thus reducing ROS and conferring resistance to ROS-mediated apoptosis.\",\n      \"method\": \"Jdp2 KO mice, primary GCP cultures, ChIP, co-immunoprecipitation, ROS measurement, apoptosis assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus co-IP plus KO phenotype, single lab\",\n      \"pmids\": [\"32188872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"JDP2 forms an activation complex with AHR-ARNT and NRF2-sMAF at dioxin response elements (DRE) and antioxidant response elements (ARE) in the AHR promoter in response to DMSO, regulating AHR promoter activity and ROS production. Jdp2 is required for AHR promoter activation; co-immunoprecipitation and ChIP confirmed JDP2 presence in the complex at DRE sites.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, promoter reporter assay, Jdp2 KO MEFs, DMSO treatment\",\n      \"journal\": \"Cell biology and toxicology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus ChIP plus KO, single lab, multiple methods\",\n      \"pmids\": [\"33723743\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"JDP2 is directly regulated at the transcriptional level by ATF4; JDP2 knockdown enhances expression of ATF4 target genes including ASNS, DR4, and DR5. JDP2 overexpression represses ER stress-mediated DR5 promoter activation (transient reporter assay). JDP2 knockdown increases TRAIL sensitivity in HeLa cells, indicating JDP2 functions as a negative feedback regulator of the ATF4 pathway to confer TRAIL resistance.\",\n      \"method\": \"siRNA knockdown, reporter assay, western blot, TRAIL sensitivity assay\",\n      \"journal\": \"FEBS open bio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA KD plus reporter assay plus functional TRAIL assay, single lab\",\n      \"pmids\": [\"33108704\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"JDP2 directly interacts with p53 via its C-terminal domain (confirmed by co-IP and domain mapping). JDP2 enhances p53 transactivation in p53-null H1299 cells reconstituted with WT p53 but fails to enhance transactivation of hotspot mutant p53. JDP2 reduces MDM2 levels to enhance p53 transactivation, and slightly stabilizes p53 in CHX chase experiments.\",\n      \"method\": \"Co-immunoprecipitation, domain deletion analysis, reporter assay (p53 14X RE-Luc), CHX chase, western blot\",\n      \"journal\": \"Cancers\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus reporter assay plus CHX chase, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"38473360\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"p53 significantly represses the transcriptional activity of the JDP2 promoter, suggesting a negative feedback loop between JDP2 (which represses p53) and p53 (which represses JDP2).\",\n      \"method\": \"Promoter cloning, reporter assay, primer extension analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reporter assay with promoter mapping, single lab, single method\",\n      \"pmids\": [\"25026555\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"JDP2 transcriptionally suppresses ITGBL1 promoter activity (dual-luciferase assay); ITGBL1 overexpression reverses the effects of JDP2 upregulation on pancreatic cancer cell proliferation, migration, and invasion.\",\n      \"method\": \"Dual-luciferase reporter assay, gain/loss-of-function, cell proliferation and invasion assays\",\n      \"journal\": \"Brazilian journal of medical and biological research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single reporter assay plus overexpression rescue, single lab\",\n      \"pmids\": [\"35584452\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"JDP2 directly activates PDE4B transcription in cardiomyocytes (confirmed by dual-luciferase reporter and ChIP assays); JDP2 overexpression upregulates PDE4B expression and exacerbates hypoxia/reoxygenation-induced H9c2 cell injury.\",\n      \"method\": \"Dual-luciferase reporter assay, ChIP, overexpression, hypoxia/reoxygenation model\",\n      \"journal\": \"Experimental and therapeutic medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — ChIP plus reporter assay, single lab\",\n      \"pmids\": [\"35401806\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"IRF2BP2 interacts with the AP-1 heterodimer ATF7/JDP2, is recruited to chromatin by ATF7/JDP2, and counteracts its gene-activating function in AML cells. Loss of IRF2BP2 leads to overactivation of inflammatory pathways driven by ATF7/JDP2.\",\n      \"method\": \"Co-immunoprecipitation, ChIP-seq, loss-of-function (IRF2BP2 KO), gene expression analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus ChIP plus KO with transcriptome readout, single lab\",\n      \"pmids\": [\"38801077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"A combination of Jdp2 with six other factors (Jhdm1b, Mkk6, Glis1, Nanog, Essrb, Sall4) can reprogram mouse embryonic fibroblasts to chimera-competent iPSCs. ATAC-seq and RNA-seq reveal that Jdp2 participates in dynamically closing and opening chromatin loci as part of a cooperative reprogramming process.\",\n      \"method\": \"Reprogramming assay, RNA-seq, ATAC-seq, chimera injection, dropout experiments\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional reprogramming with ATAC-seq chromatin analysis, single lab\",\n      \"pmids\": [\"31216469\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CGRP suppresses β-glucan-induced inflammation and osteoclast multinucleation via direct suppression of NF-κB p65 by the transcriptional repressor Jdp2.\",\n      \"method\": \"In vivo nociceptor ablation, TRPV1/TRPA1 knockout, CGRP treatment, inflammatory readout, mechanistic pathway dissection\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo genetic KO with pathway dissection, single lab\",\n      \"pmids\": [\"28658621\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"JDP2 is a bZIP transcriptional repressor (and context-dependent activator) of AP-1 target genes that acts through multiple chromatin-level mechanisms: it recruits HDAC3 to promoters to repress histone acetylation, directly inhibits p300-mediated histone acetylation via an N-terminal INHAT domain, and exhibits histone-chaperone activity; it is phosphorylated on Thr148 by JNK, which targets it for proteasomal degradation; it forms functional heterodimers with Jun/ATF2, CHOP10, and ATF7, and interacts with partners including p53, progesterone receptor (via the CTE), and IRF2BP1 (a JDP2 ubiquitin ligase); and it controls diverse biological programs including osteoclastogenesis, neutrophil differentiation, adipogenesis, myogenesis, cellular senescence (via epigenetic regulation of p16Ink4a/Arf through Polycomb complexes), cell-cycle progression (via Cyclin-A2 repression), FSHβ transcription, EBV latency, and redox homeostasis (via the β-catenin/JDP2/PRMT5 complex and the AHR-NRF2-JDP2 axis).\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"JDP2 is a bZIP transcription factor that binds AP-1/ATF-CRE cis-elements and acts predominantly as a transcriptional repressor through chromatin-level mechanisms, thereby controlling differentiation, proliferation, stress responses, and redox homeostasis across multiple lineages [#0, #6, #8]. It represses target promoters by recruiting an HDAC3 complex and by directly inhibiting p300-mediated acetylation of core histones through its N-terminal region and DNA-binding domain, activities complemented by intrinsic histone-chaperone (nucleosome-assembly) activity [#0, #1]. Through these mechanisms JDP2 suppresses c-jun, ATF3, cyclin-A2, C/EBPδ, and CHOP transcription, and silences higher-order chromatin states such as Polycomb-mediated repression of the p16Ink4a/p19Arf locus, with corresponding control of retinoic-acid differentiation, osteoclastogenesis and neutrophil differentiation, adipogenesis, cell-cycle progression, and replicative senescence [#0, #6, #7, #8, #9, #16]. JDP2 activity is gated by JNK, which phosphorylates Thr148 to target the protein for proteasomal degradation, and by the RING-finger ubiquitin ligase IRF2BP1 [#2, #3, #15]. Its DNA-binding specificity and transcriptional output are tuned by partner exchange: it heterodimerizes with c-JUN, ATF7, CHOP10, and ATF2, and interacts with the progesterone receptor, p53, and chromatin-modifying complexes [#12, #13, #20, #26, #30]. JDP2 also functions in genotoxic and oxidative stress: ATM-phosphorylated JDP2 nucleates a β-catenin/JDP2/PRMT5 complex that recruits WDR5/MLL to install activating histone methylation at glutathione-metabolic genes, restoring redox balance [#19]. In disease contexts it represses Trp53 and activates MCL1 to promote leukemic survival and steroid resistance [#17, #18].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing how JDP2 is regulated post-translationally, JNK was shown to directly phosphorylate JDP2 at a defined residue, placing it downstream of stress kinase signaling.\",\n      \"evidence\": \"In vitro and in vivo kinase assays with T148A mutagenesis\",\n      \"pmids\": [\"11602244\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of Thr148 phosphorylation not resolved here\", \"Identity of the relevant JNK isoform not defined\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"JDP2 was placed in the survival pathway by showing it represses the p53 promoter through an atypical AP-1 site, defining an early transcriptional-repressor function.\",\n      \"evidence\": \"Reporter assay and UV-induced cell viability with overexpression\",\n      \"pmids\": [\"11287607\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct DNA-binding/occupancy confirmation at the endogenous promoter\", \"Physiological relevance beyond UV challenge unclear\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"The core repression mechanism was defined: JDP2 recruits HDAC3 to a target promoter and is displaced by p300 upon differentiation cues, linking JDP2 to dynamic histone acetylation control.\",\n      \"evidence\": \"ChIP, co-IP, and reporter assays in RA-treated F9 cells\",\n      \"pmids\": [\"12052888\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical interaction surface with HDAC3 not mapped\", \"Generality across other promoters not yet shown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"JDP2 was shown to act intrinsically on chromatin — directly inhibiting p300 acetyltransferase activity and assembling nucleosomes — establishing it as a bona fide chromatin regulator, not merely a DNA-binding adaptor.\",\n      \"evidence\": \"In vitro/in vivo acetylation assays, nucleosome assembly assay, deletion mutagenesis\",\n      \"pmids\": [\"16518400\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of INHAT-like inhibition not solved\", \"Relative in vivo contribution of HDAC recruitment vs direct p300 inhibition unquantified\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Linking the chromatin mechanism to a developmental program, JDP2 was shown to restrain adipogenesis by deacetylating the C/EBPδ promoter.\",\n      \"evidence\": \"Jdp2 KO MEFs, ChIP for H3 acetylation, adipocyte differentiation and reporter assays\",\n      \"pmids\": [\"17464331\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream signals controlling JDP2 at this locus not defined\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Partner-dependent functional switching was demonstrated: heterodimerization with CHOP10 converts JDP2 into a TRE-selective activator that opposes CHOP10-driven apoptosis under ER stress.\",\n      \"evidence\": \"Co-IP, EMSA, ChIP, reporter and viability assays\",\n      \"pmids\": [\"18463134\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo relevance of the JDP2-CHOP10 complex not tested\", \"Determinants of TRE vs CRE selectivity incompletely defined\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"A degradation route was added by identifying IRF2BP1 as a RING-finger ubiquitin ligase for JDP2, defining a JNK-independent control of JDP2 levels.\",\n      \"evidence\": \"Tagged pulldown, polyubiquitination and reporter assays\",\n      \"pmids\": [\"18671972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single pulldown without reciprocal validation\", \"Endogenous regulation and physiological context unaddressed\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"JDP2 was connected to senescence control, showing its absence permits Polycomb (PRC1/PRC2) repression of p16Ink4a, defining an epigenetic gatekeeper role.\",\n      \"evidence\": \"Jdp2 KO MEFs, ChIP for H3K27me and PRC binding, overexpression\",\n      \"pmids\": [\"19233846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which JDP2 antagonizes PRC recruitment unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Direct promoter occupancy at consensus and non-consensus sites was demonstrated for ATF3 repression, and structural mapping defined how JDP2 engages the progesterone receptor CTE to modulate its activity.\",\n      \"evidence\": \"KO/transgenic mice with reporter assays (ATF3); NMR chemical-shift mapping and CTE swaps (PR)\",\n      \"pmids\": [\"19233874\", \"19553667\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether PR enhancement uses the same chromatin machinery as repression unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"A proliferation-control axis was established by showing JDP2 occupies and represses the cyclin-A2 promoter in vivo, restraining cell-cycle progression.\",\n      \"evidence\": \"Jdp2 KO mice, ChIP, qRT-PCR, rescue re-expression\",\n      \"pmids\": [\"20802531\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Coordination with other cell-cycle targets not mapped\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"The fate of Thr148 phosphorylation was resolved: it targets JDP2 for proteasomal degradation, coupling stress-kinase signaling to JDP2 turnover.\",\n      \"evidence\": \"Phospho-mimetic/non-phosphorylatable mutants, kinase/proteasome inhibitors, CHX chase\",\n      \"pmids\": [\"21463260\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The ubiquitin ligase acting on phospho-JDP2 not identified in this study\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"JDP2 was shown to maintain viral latency, binding the EBV BZLF1 promoter with HDAC3 to suppress lytic reactivation.\",\n      \"evidence\": \"EMSA, ChIP, RNAi, mutant virus analysis\",\n      \"pmids\": [\"21525011\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Host signals that relieve JDP2 repression during reactivation undefined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"In vivo KO confirmed JDP2's developmental roles, showing osteopetrosis from impaired osteoclastogenesis and defective neutrophil differentiation via histone-acetylation-dependent ATF3 suppression.\",\n      \"evidence\": \"Jdp2 KO mice, bone histology, neutrophil assays, ChIP\",\n      \"pmids\": [\"23200825\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Cell-autonomous vs niche contributions to bone phenotype not fully separated\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"A genotoxic-stress redox function was defined: ATM-phosphorylated JDP2 nucleates a β-catenin/PRMT5 complex recruiting WDR5/MLL to activate glutathione-metabolic genes, showing JDP2 can also drive activating histone methylation.\",\n      \"evidence\": \"Co-IP, ChIP, histone-modification assays, WDR5 inhibitor (OICR-9429)\",\n      \"pmids\": [\"31434880\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"ATM phosphosite on JDP2 not mapped\", \"Switch between repressive and activating modes mechanistically unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"An oncogenic survival role was established in T-ALL, where JDP2 activates MCL1 to confer apoptosis resistance and steroid resistance.\",\n      \"evidence\": \"shRNA knockdown, transgenic zebrafish, gene expression\",\n      \"pmids\": [\"29941549\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct promoter occupancy at MCL1 not fully demonstrated\", \"Cofactor dependence in leukemic cells unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Refining the JDP2-p53 relationship, JDP2 was shown to bind p53 via its C-terminus, lower MDM2, and enhance WT (but not mutant) p53 transactivation, indicating context-dependent activation rather than uniform repression.\",\n      \"evidence\": \"Co-IP, domain mapping, p53 reporter, CHX chase\",\n      \"pmids\": [\"38473360\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reconciliation with earlier Trp53-promoter repression unresolved\", \"Mechanism of MDM2 reduction undefined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Partner-specific corepression was mapped in AML, where IRF2BP2 is recruited by the ATF7/JDP2 heterodimer to chromatin and restrains its inflammatory gene-activating output.\",\n      \"evidence\": \"Co-IP, ChIP-seq, IRF2BP2 KO with transcriptomics\",\n      \"pmids\": [\"38801077\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether ATF7/JDP2 activates or represses depends on cofactor balance not fully defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How JDP2 toggles between repressive (HDAC3/p300-inhibition) and activating (PRMT5/WDR5/MLL, CHOP10, p53) chromatin outputs at a given locus — and how this is set by partner identity, post-translational modification, and stress state — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking dimer partner to activation vs repression\", \"No structural model of the JDP2 chromatin-modifying complexes\", \"Phosphosites beyond Thr148 and their ligases incompletely defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 6, 8, 11, 12, 20]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [1, 11, 12, 16, 20]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 8, 19]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [7, 19]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 6, 8, 11]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 7, 19]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [8, 10]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [12, 16, 19, 25]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [6, 9, 10]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [12, 18, 25]}\n    ],\n    \"complexes\": [\n      \"JDP2/HDAC3 corepressor complex\",\n      \"JDP2-CHOP10 heterodimer\",\n      \"β-catenin/JDP2/PRMT5 complex\",\n      \"ATF7/JDP2 AP-1 heterodimer\"\n    ],\n    \"partners\": [\n      \"HDAC3\",\n      \"EP300\",\n      \"CHOP10/DDIT3\",\n      \"JUN\",\n      \"ATF7\",\n      \"PRMT5\",\n      \"IRF2BP1\",\n      \"TP53\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}