{"gene":"PSMD7","run_date":"2026-04-28T19:45:45","timeline":{"discoveries":[{"year":1998,"finding":"PSMD7 (hVIP/MOV34), a 34-kDa member of the MOV34 family and component of the 26S proteasome 19S regulatory complex, was identified as a direct binding partner of HIV-1 Vpr by yeast two-hybrid assay and confirmed by in vitro and in vivo co-immunoprecipitation. hVIP/MOV34 localizes to the nucleus and its subcellular localization shifts from nuclear to perinuclear upon Vpr-induced G2/M cell-cycle arrest, coinciding with inhibition of MPF-associated histone H1 kinase activity, indicating a functional role in cell-cycle regulation.","method":"Yeast two-hybrid, in vitro binding assay, in vivo co-immunoprecipitation, immunofluorescence localization, histone H1 kinase activity assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2-3 — reciprocal binding confirmed in vitro and in vivo, localization tied to functional phenotype, but single lab","pmids":["9520381"],"is_preprint":false},{"year":1998,"finding":"Human PSMD7 (p40.5) was cloned and identified as a non-ATPase subunit of the PA700 (19S) regulatory complex of the 26S proteasome, homologous to yeast Nas7p. Disruption of the yeast NAS7 gene caused hypersensitivity to heat stress (inability to grow at 37°C), while NAS6 disruption had no effect, demonstrating that Nas7p/PSMD7 is required for normal proteasome function under stress conditions.","method":"cDNA cloning, sequence homology analysis, yeast gene disruption with phenotypic readout (heat-stress sensitivity)","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 — genetic loss-of-function in yeast ortholog with defined phenotype; single study","pmids":["9714768"],"is_preprint":false},{"year":2002,"finding":"The carboxyl-terminal domain of hVIP/MOV34 (PSMD7) is critical for its interaction with HIV-1 Vpr, as C-terminal deletion mutants abolish both Vpr binding and Vpr-induced nuclear relocalization of hVIP. Full-length hVIP is cytoplasmic but translocates to the nucleus in the presence of Vpr or dexamethasone; C-terminal mutants are unresponsive to both Vpr and glucocorticoids, linking PSMD7's C-terminus to glucocorticoid receptor signaling.","method":"Deletion mutagenesis, co-immunoprecipitation, immunofluorescence localization, pharmacological manipulation (dexamethasone/glucocorticoid antagonist)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2-3 — domain mapping with mutagenesis and functional localization readout; single lab","pmids":["12237292"],"is_preprint":false},{"year":2007,"finding":"The crystal structure of the MPN domain of human PSMD7 (Mov34) was solved at 1.96 Å resolution and revealed a nine-β-strand/three-α-helix fold with a domain-swap dimer in solution. Unlike the catalytically active JAMM/MPN+ domains of Rpn11 (PSMD14) and Csn5, the PSMD7 MPN domain lacks the zinc-coordinating residues required for metalloprotease activity (the JAMM motif is degenerate), explaining why PSMD7 has no isopeptidase activity and instead serves a structural role within the 19S proteasome lid.","method":"X-ray crystallography (1.96 Å and 3.0 Å), size-exclusion chromatography, dynamic light scattering, amino acid sequence comparison","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 — high-resolution crystal structure with biophysical validation and functional inference from active-site analysis","pmids":["17559875"],"is_preprint":false},{"year":2014,"finding":"Crystal structures of the yeast Rpn8-Rpn11 MPN-domain heterodimer (the ortholog of human PSMD7-PSMD14) at 2.0 Å revealed that Rpn8 (PSMD7 ortholog) forms two distinct interfaces with the catalytically active Rpn11 (PSMD14 ortholog). Rpn8 is required to stabilize Rpn11 in the heterodimer; structural and mutational analysis showed that Rpn11 lacks a conserved surface for ubiquitin Ile44-patch binding and exhibits no linkage specificity, functioning as a promiscuous deubiquitinase for co-translocation substrate deubiquitination.","method":"X-ray crystallography (2.0 Å), in vitro deubiquitinase activity assay, site-directed mutagenesis","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 — high-resolution structure combined with in vitro enzymatic assay and mutagenesis in a single rigorous study","pmids":["24463465"],"is_preprint":false},{"year":2014,"finding":"Crystal structures of the Rpn8-Rpn11 heterodimer (human PSMD7-PSMD14 orthologs) showed that full DUB activation of Rpn11 requires its incorporation into the 26S proteasome and is dependent on ATP hydrolysis, suggesting coupling of substrate processing with ubiquitin removal. An insertion segment in Rpn11 acts as a physical barrier across the substrate access channel and a conformationally unstable catalytic loop prevent premature deubiquitination; contacts with ATPase subunits (observed by docking into EM density) stabilize the active conformation. Rpn8 (PSMD7) contributes structurally to forming the active heterodimer.","method":"X-ray crystallography, nanobody-assisted crystallization, in vitro DUB activity assay, EM density docking","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 — multiple orthogonal structural and biochemical methods; independently replicates Rpn8-Rpn11 heterodimer findings from companion paper","pmids":["24516147"],"is_preprint":false},{"year":2009,"finding":"Global proteomic analysis of deubiquitinase-associated complexes confirmed that PSMD7 (as part of the 19S proteasome lid) is a component of the deubiquitinase interaction landscape, associating with the 26S proteasome complex including PSMD14 and other 19S regulatory particle subunits.","method":"Affinity purification–mass spectrometry (AP-MS) with CompPASS scoring","journal":"Cell","confidence":"Medium","confidence_rationale":"Tier 2 — large-scale AP-MS with computational confidence scoring; confirms complex membership but not mechanistic detail specific to PSMD7","pmids":["19615732"],"is_preprint":false},{"year":2018,"finding":"PSMD7 knockdown in esophageal squamous cell carcinoma (EC9706) cells decreased proliferation, increased apoptosis, reduced proteasomal function, and suppressed mTOR/p70S6K pathway activity (lower p-mTOR Ser2448 and p-p70S6K Thr421/Ser424). Conversely, PSMD7 overexpression in Het-1A cells increased phosphorylation of mTOR and p70S6K, placing PSMD7 upstream of mTOR/p70S6K signaling. In vivo xenograft experiments confirmed decelerated tumor growth upon PSMD7 knockdown with attenuated mTOR/p70S6K signaling.","method":"Lentivirus-mediated shRNA knockdown, overexpression, Western blotting for pathway components, cell proliferation/apoptosis assays, in vivo xenograft","journal":"FEBS open bio","confidence":"Medium","confidence_rationale":"Tier 2-3 — loss- and gain-of-function with defined molecular readout; single lab, pathway placement via phospho-protein analysis","pmids":["29632807"],"is_preprint":false},{"year":2021,"finding":"PSMD7 functions as a deubiquitinase in gastric cancer cells, directly interacting with RAD23B (confirmed by co-immunoprecipitation) and stabilizing RAD23B protein by preventing its ubiquitin-mediated proteasomal degradation. PSMD7 knockdown enhanced RAD23B ubiquitination and degradation, reduced XPC protein levels (a RAD23B-dependent DNA repair factor), suppressed proliferation/invasion, increased cisplatin sensitivity, and inhibited tumor growth in vivo, defining the PSMD7–RAD23B–XPC axis as a mechanism of chemotherapy resistance.","method":"Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, overexpression, cell viability/apoptosis/DNA damage repair assays, in vivo xenograft","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP confirms binding, ubiquitination assay establishes DUB substrate relationship, multiple functional readouts; single lab","pmids":["34512150"],"is_preprint":false},{"year":2024,"finding":"PSMD7 deubiquitinates and stabilizes SOX2 protein in pancreatic cancer cells, preventing its proteasomal degradation. Stabilized SOX2 activates the Notch1 signaling pathway, promoting pancreatic cancer cell proliferation and invasion. Restoration of SOX2 expression rescued the antitumor effect of PSMD7 silencing, placing PSMD7 upstream of SOX2–Notch1 in pancreatic cancer progression.","method":"In vitro and in vivo gain/loss-of-function assays, co-immunoprecipitation, ubiquitination assay, rescue experiments with SOX2 re-expression, Notch1 pathway reporter analysis","journal":"Cell & bioscience","confidence":"Medium","confidence_rationale":"Tier 2-3 — epistasis via rescue experiment, Co-IP and ubiquitination assay define DUB-substrate relationship; single lab","pmids":["38494478"],"is_preprint":false}],"current_model":"PSMD7 (Mov34/hVIP) is a non-catalytic MPN-domain subunit of the 26S proteasome 19S regulatory lid that forms an obligate structural heterodimer with the active deubiquitinase PSMD14 (Rpn11); PSMD7's degenerate JAMM motif renders it catalytically inactive for isopeptide-bond cleavage, but it stabilizes and activates PSMD14 within the lid complex, and in cancer contexts PSMD7 itself exhibits deubiquitinase activity toward substrates RAD23B and SOX2, stabilizing them to promote proliferation, chemoresistance, and Notch1 signaling, while also interacting with HIV-1 Vpr to modulate cell-cycle progression."},"narrative":{"teleology":[{"year":1998,"claim":"Identification of PSMD7 as a 26S proteasome 19S regulatory subunit and HIV-1 Vpr interactor established its dual role in proteasome biology and viral exploitation of the cell cycle.","evidence":"Yeast two-hybrid, co-immunoprecipitation, yeast NAS7 gene disruption with heat-stress phenotype","pmids":["9520381","9714768"],"confidence":"Medium","gaps":["Mechanism by which Vpr–PSMD7 interaction triggers G2/M arrest not defined","Whether PSMD7 has proteasome-independent functions in cell-cycle control unclear"]},{"year":2002,"claim":"Mapping the Vpr-binding determinant to PSMD7's C-terminal domain and linking this region to glucocorticoid receptor–mediated nuclear import revealed a domain-specific mechanism for PSMD7 relocalization.","evidence":"Deletion mutagenesis, co-immunoprecipitation, immunofluorescence with dexamethasone and glucocorticoid antagonist treatments","pmids":["12237292"],"confidence":"Medium","gaps":["No direct binding between PSMD7 C-terminus and glucocorticoid receptor shown","Functional consequence of nuclear relocalization on proteasome activity not tested"]},{"year":2007,"claim":"The crystal structure of the PSMD7 MPN domain resolved why it lacks isopeptidase activity: its degenerate JAMM motif cannot coordinate the catalytic zinc ion, establishing PSMD7 as a structural rather than enzymatic MPN subunit.","evidence":"X-ray crystallography at 1.96 Å, size-exclusion chromatography, sequence comparison with catalytically active JAMM domains","pmids":["17559875"],"confidence":"High","gaps":["Structure of full-length PSMD7 not determined","Contribution of non-MPN regions to proteasome lid assembly unknown"]},{"year":2014,"claim":"High-resolution structures of the PSMD7–PSMD14 (Rpn8–Rpn11) heterodimer demonstrated that PSMD7 is an obligate activating partner of PSMD14, and that full deubiquitinase activation requires incorporation into the 26S proteasome and is coupled to ATP hydrolysis.","evidence":"X-ray crystallography at 2.0 Å, in vitro DUB activity assays, site-directed mutagenesis, EM density docking (two independent studies)","pmids":["24463465","24516147"],"confidence":"High","gaps":["Conformational dynamics of the insertion-loop gating mechanism not resolved at atomic level in the intact 26S context","Contribution of individual PSMD7–PSMD14 interfaces to lid assembly versus DUB activation not dissected"]},{"year":2018,"claim":"Functional studies in esophageal cancer showed PSMD7 knockdown impairs proteasome function and suppresses mTOR/p70S6K signaling, linking proteasome subunit stoichiometry to growth-factor pathway output.","evidence":"Lentiviral shRNA knockdown and overexpression, phospho-Western blotting, in vivo xenograft","pmids":["29632807"],"confidence":"Medium","gaps":["Whether mTOR/p70S6K effects are specific to PSMD7 or secondary to general proteasome impairment not distinguished","No proteasome activity quantification beyond pathway phospho-readouts"]},{"year":2021,"claim":"Discovery that PSMD7 directly deubiquitinates and stabilizes RAD23B, thereby maintaining XPC-dependent DNA repair and conferring cisplatin resistance, revealed an unexpected substrate-directed DUB function for a supposedly catalytically inactive MPN subunit.","evidence":"Co-immunoprecipitation, in vivo ubiquitination assay, shRNA knockdown/overexpression, cisplatin sensitivity assays, xenograft","pmids":["34512150"],"confidence":"Medium","gaps":["Direct isopeptidase activity of PSMD7 on RAD23B not reconstituted with purified recombinant protein","Whether DUB activity is intrinsic to PSMD7 or mediated through co-purifying PSMD14 not excluded","Not independently replicated"]},{"year":2024,"claim":"Extension of the DUB paradigm to SOX2 in pancreatic cancer, with epistasis rescue experiments placing PSMD7 upstream of SOX2–Notch1 signaling, broadened the substrate repertoire attributed to PSMD7.","evidence":"Co-immunoprecipitation, ubiquitination assay, SOX2 rescue experiments, Notch1 pathway reporter assays, in vivo xenograft","pmids":["38494478"],"confidence":"Medium","gaps":["In vitro reconstitution of PSMD7-catalyzed SOX2 deubiquitination not performed","Catalytic residues responsible for DUB activity not identified given the degenerate JAMM motif","Whether PSMD14 co-purifies in cancer-context immunoprecipitates not controlled"]},{"year":null,"claim":"The central unresolved question is whether the reported DUB activity toward RAD23B and SOX2 is intrinsic to PSMD7 or mediated by co-purifying PSMD14, given that structural data show PSMD7 lacks the canonical catalytic zinc site.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Reconstitution of purified recombinant PSMD7 DUB activity in vitro is needed","Catalytic-site mutagenesis in PSMD7 to abolish reported DUB activity not performed","Proteasome-independent versus proteasome-dependent roles of PSMD7 in cancer not delineated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[3,4,5]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[8,9]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2,6]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[3,4,5,6]}],"complexes":["26S proteasome 19S regulatory particle (lid)"],"partners":["PSMD14","RAD23B","SOX2","HIV-1 VPR"],"other_free_text":[]},"mechanistic_narrative":"PSMD7 is a non-catalytic MPN-domain subunit of the 26S proteasome 19S regulatory particle lid that forms an obligate heterodimer with the deubiquitinase PSMD14 (Rpn11), stabilizing and activating PSMD14's isopeptidase function during substrate translocation [PMID:24463465, PMID:24516147]. The PSMD7 MPN domain contains a degenerate JAMM motif lacking zinc-coordinating residues essential for metalloprotease activity, rendering it catalytically inactive as an isopeptidase and assigning it a primarily structural role within the lid [PMID:17559875]. Its yeast ortholog Nas7p is required for proteasome function under stress [PMID:9714768], and PSMD7 interacts with HIV-1 Vpr through its C-terminal domain, linking it to Vpr-induced G2/M arrest [PMID:9520381, PMID:12237292]. In cancer contexts, PSMD7 has been reported to deubiquitinate and stabilize RAD23B and SOX2, promoting chemoresistance via the RAD23B–XPC DNA-repair axis and activating Notch1 signaling through SOX2, respectively [PMID:34512150, PMID:38494478]."},"prefetch_data":{"uniprot":{"accession":"P51665","full_name":"26S proteasome non-ATPase regulatory subunit 7","aliases":["26S proteasome regulatory subunit RPN8","26S proteasome regulatory subunit S12","Mov34 protein homolog","Proteasome subunit p40"],"length_aa":324,"mass_kda":37.0,"function":"Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/P51665/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/PSMD7","classification":"Common Essential","n_dependent_lines":1206,"n_total_lines":1208,"dependency_fraction":0.9983443708609272},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000103035","cell_line_id":"CID000120","localizations":[{"compartment":"nucleoplasm","grade":3},{"compartment":"big_aggregates","grade":2},{"compartment":"cytoplasmic","grade":2}],"interactors":[{"gene":"PSMC4","stoichiometry":10.0},{"gene":"PSMC6","stoichiometry":10.0},{"gene":"PSMD12","stoichiometry":10.0},{"gene":"PSMD2","stoichiometry":10.0},{"gene":"PSMC1","stoichiometry":10.0},{"gene":"PSMC5","stoichiometry":10.0},{"gene":"PSMD6","stoichiometry":10.0},{"gene":"PSMD13","stoichiometry":10.0},{"gene":"PSMC3","stoichiometry":10.0},{"gene":"PSMD1","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000120","total_profiled":1310},"omim":[{"mim_id":"614729","title":"COP9 SIGNALOSOME, SUBUNIT 6; COPS6","url":"https://www.omim.org/entry/614729"},{"mim_id":"607173","title":"PROTEASOME 26S SUBUNIT, NON-ATPase, 14; PSMD14","url":"https://www.omim.org/entry/607173"},{"mim_id":"604850","title":"COP9 SIGNALOSOME, SUBUNIT 5; COPS5","url":"https://www.omim.org/entry/604850"},{"mim_id":"157970","title":"PROTEASOME 26S SUBUNIT, NON-ATPase, 7; PSMD7","url":"https://www.omim.org/entry/157970"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Acrosome","reliability":"Approved"},{"location":"Equatorial segment","reliability":"Approved"},{"location":"Mid piece","reliability":"Approved"},{"location":"Principal piece","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PSMD7"},"hgnc":{"alias_symbol":["S12","P40","MOV34","Rpn8"],"prev_symbol":[]},"alphafold":{"accession":"P51665","domains":[{"cath_id":"3.40.140.10","chopping":"7-180","consensus_level":"high","plddt":85.8417,"start":7,"end":180},{"cath_id":"1.20.5","chopping":"184-237","consensus_level":"medium","plddt":85.8972,"start":184,"end":237},{"cath_id":"1.20.5","chopping":"240-291","consensus_level":"medium","plddt":89.2463,"start":240,"end":291}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P51665","model_url":"https://alphafold.ebi.ac.uk/files/AF-P51665-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P51665-F1-predicted_aligned_error_v6.png","plddt_mean":83.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PSMD7","jax_strain_url":"https://www.jax.org/strain/search?query=PSMD7"},"sequence":{"accession":"P51665","fasta_url":"https://rest.uniprot.org/uniprotkb/P51665.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P51665/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P51665"}},"corpus_meta":[{"pmid":"14707118","id":"PMC_14707118","title":"Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris.","date":"2004","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/14707118","citation_count":718,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8551218","id":"PMC_8551218","title":"The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells.","date":"1996","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/8551218","citation_count":544,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7565674","id":"PMC_7565674","title":"Regulation of interleukin 12 p40 expression through an NF-kappa B half-site.","date":"1995","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/7565674","citation_count":413,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7843232","id":"PMC_7843232","title":"Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist.","date":"1995","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/7843232","citation_count":399,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7527811","id":"PMC_7527811","title":"Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity.","date":"1995","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/7527811","citation_count":353,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7605994","id":"PMC_7605994","title":"Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes.","date":"1995","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/7605994","citation_count":308,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22056955","id":"PMC_22056955","title":"p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma.","date":"2011","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/22056955","citation_count":307,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12952918","id":"PMC_12952918","title":"Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells.","date":"2003","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/12952918","citation_count":286,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8551575","id":"PMC_8551575","title":"A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes.","date":"1996","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/8551575","citation_count":285,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8103745","id":"PMC_8103745","title":"The interleukin-12 subunit p40 specifically inhibits effects of the interleukin-12 heterodimer.","date":"1993","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/8103745","citation_count":275,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3137580","id":"PMC_3137580","title":"Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity.","date":"1988","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/3137580","citation_count":275,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11058167","id":"PMC_11058167","title":"Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages.","date":"2000","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11058167","citation_count":240,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8955413","id":"PMC_8955413","title":"Induction of actinorhodin production by rpsL (encoding ribosomal protein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2).","date":"1996","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/8955413","citation_count":190,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9127002","id":"PMC_9127002","title":"In vivo production and function of IL-12 p40 homodimers.","date":"1997","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/9127002","citation_count":184,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12552125","id":"PMC_12552125","title":"The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12552125","citation_count":170,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24463465","id":"PMC_24463465","title":"Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate deubiquitination during proteasomal degradation.","date":"2014","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/24463465","citation_count":131,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10362802","id":"PMC_10362802","title":"Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer.","date":"1999","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/10362802","citation_count":118,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12456638","id":"PMC_12456638","title":"The adaptor protein p40(phox) as a positive regulator of the superoxide-producing phagocyte oxidase.","date":"2002","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/12456638","citation_count":117,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24516147","id":"PMC_24516147","title":"Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24516147","citation_count":113,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10485447","id":"PMC_10485447","title":"Mutational analysis of the p63/p73L/p51/p40/CUSP/KET gene in human cancer cell lines using intronic primers.","date":"1999","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/10485447","citation_count":113,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2477554","id":"PMC_2477554","title":"Mutations in ribosomal proteins S4 and S12 influence the higher order structure of 16 S ribosomal RNA.","date":"1989","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/2477554","citation_count":112,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24895124","id":"PMC_24895124","title":"Activation of epidermal growth factor receptor mediates mucin production stimulated by p40, a Lactobacillus rhamnosus GG-derived protein.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24895124","citation_count":105,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2033660","id":"PMC_2033660","title":"Sequences required for coordinate induction of adeno-associated virus p19 and p40 promoters by Rep protein.","date":"1991","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/2033660","citation_count":99,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23784800","id":"PMC_23784800","title":"Role of anthocyanin-enriched purple-fleshed sweet potato p40 in colorectal cancer prevention.","date":"2013","source":"Molecular nutrition & food research","url":"https://pubmed.ncbi.nlm.nih.gov/23784800","citation_count":99,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8557986","id":"PMC_8557986","title":"Herpes simplex virus type 1-mediated up-regulation of IL-12 (p40) mRNA expression. Implications in immunopathogenesis and protection.","date":"1996","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/8557986","citation_count":98,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17967466","id":"PMC_17967466","title":"Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome.","date":"2007","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17967466","citation_count":97,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"14679201","id":"PMC_14679201","title":"Inhibition of interleukin-12 p40 transcription and NF-kappaB activation by nitric oxide in murine macrophages and dendritic cells.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14679201","citation_count":94,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18252828","id":"PMC_18252828","title":"RimO, a MiaB-like enzyme, methylthiolates the universally conserved Asp88 residue of ribosomal protein S12 in Escherichia coli.","date":"2008","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/18252828","citation_count":92,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21383239","id":"PMC_21383239","title":"NFIL3 is a regulator of IL-12 p40 in macrophages and mucosal immunity.","date":"2011","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/21383239","citation_count":92,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9520381","id":"PMC_9520381","title":"HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle.","date":"1998","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/9520381","citation_count":91,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12100467","id":"PMC_12100467","title":"IL-12: the role of p40 versus p75.","date":"2002","source":"Scandinavian journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12100467","citation_count":86,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21178363","id":"PMC_21178363","title":"Functional analysis of the p40 and p75 proteins from Lactobacillus casei BL23.","date":"2010","source":"Journal of molecular microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/21178363","citation_count":85,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16263713","id":"PMC_16263713","title":"Mycobacterium tuberculosis lipoarabinomannan-mediated IRAK-M induction negatively regulates Toll-like receptor-dependent interleukin-12 p40 production in macrophages.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16263713","citation_count":85,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16342235","id":"PMC_16342235","title":"Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns.","date":"2006","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16342235","citation_count":83,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"14993278","id":"PMC_14993278","title":"Interleukin-10 inhibits interleukin-12 p40 gene transcription by targeting a late event in the activation pathway.","date":"2004","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/14993278","citation_count":82,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9714768","id":"PMC_9714768","title":"cDNA cloning and functional analysis of p28 (Nas6p) and p40.5 (Nas7p), two novel regulatory subunits of the 26S proteasome.","date":"1998","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/9714768","citation_count":80,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22751010","id":"PMC_22751010","title":"Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration.","date":"2012","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/22751010","citation_count":75,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1454526","id":"PMC_1454526","title":"The mitochondrial gene encoding ribosomal protein S12 has been translocated to the nuclear genome in Oenothera.","date":"1992","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/1454526","citation_count":74,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7925572","id":"PMC_7925572","title":"Differential expression of mRNA encoding interleukin-12 p35 and p40 subunits in situ.","date":"1994","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/7925572","citation_count":72,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24047617","id":"PMC_24047617","title":"IL12/23 p40 inhibition ameliorates Alzheimer's disease-associated neuropathology and spatial memory in SAMP8 mice.","date":"2014","source":"Journal of Alzheimer's disease : JAD","url":"https://pubmed.ncbi.nlm.nih.gov/24047617","citation_count":71,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8647196","id":"PMC_8647196","title":"Structure and chromosomal location of the mouse interleukin-12 p35 and p40 subunit genes.","date":"1996","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/8647196","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15451426","id":"PMC_15451426","title":"Identification of a novel BRMS1-homologue protein p40 as a component of the mSin3A/p33(ING1b)/HDAC1 deacetylase complex.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15451426","citation_count":59,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21575643","id":"PMC_21575643","title":"Error-prone and error-restrictive mutations affecting ribosomal protein S12.","date":"2011","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/21575643","citation_count":57,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33159116","id":"PMC_33159116","title":"Lactobacillus casei extracellular vesicles stimulate EGFR pathway likely due to the presence of proteins P40 and P75 bound to their surface.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33159116","citation_count":57,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24746197","id":"PMC_24746197","title":"The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non-small cell lung cancer.","date":"2014","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/24746197","citation_count":55,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20430307","id":"PMC_20430307","title":"Anti-p40 antibodies ustekinumab and briakinumab: blockade of interleukin-12 and interleukin-23 in the treatment of psoriasis.","date":"2010","source":"Seminars in cutaneous medicine and surgery","url":"https://pubmed.ncbi.nlm.nih.gov/20430307","citation_count":51,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23221041","id":"PMC_23221041","title":"p40: a p63 isoform useful for lung cancer diagnosis - a review of the physiological and pathological role of p63.","date":"2012","source":"Acta cytologica","url":"https://pubmed.ncbi.nlm.nih.gov/23221041","citation_count":51,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9506747","id":"PMC_9506747","title":"Interleukin-12 and its free p40 subunit regulate immune recognition of endometrial cells: potential role in endometriosis.","date":"1998","source":"The Journal of clinical endocrinology and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/9506747","citation_count":51,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20449741","id":"PMC_20449741","title":"Comparative transcriptomics and proteomics of p-hydroxybenzoate producing Pseudomonas putida S12: novel responses and implications for strain improvement.","date":"2010","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/20449741","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24805133","id":"PMC_24805133","title":"p40 is the best marker for diagnosing pulmonary squamous cell carcinoma: comparison with p63, cytokeratin 5/6, desmocollin-3, and sox2.","date":"2014","source":"Applied immunohistochemistry & molecular morphology : AIMM","url":"https://pubmed.ncbi.nlm.nih.gov/24805133","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10944443","id":"PMC_10944443","title":"Characterization of p40/GPR69A as a peripheral membrane protein related to the lantibiotic synthetase component C.","date":"2000","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/10944443","citation_count":47,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"14976188","id":"PMC_14976188","title":"Activation and repression of interleukin-12 p40 transcription by erythroid Kruppel-like factor in macrophages.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14976188","citation_count":46,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1404604","id":"PMC_1404604","title":"Sequence similarity between Borna disease virus p40 and a duplicated domain within the paramyxovirus and rhabdovirus polymerase proteins.","date":"1992","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/1404604","citation_count":46,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25125621","id":"PMC_25125621","title":"Evaluation of napsin A, TTF-1, p63, p40, and CK5/6 immunohistochemical stains in pulmonary neuroendocrine tumors.","date":"2014","source":"American journal of clinical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25125621","citation_count":46,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26678060","id":"PMC_26678060","title":"IL12B (p40) Gene Polymorphisms Contribute to Ustekinumab Response Prediction in Psoriasis.","date":"2015","source":"Dermatology (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/26678060","citation_count":44,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19100623","id":"PMC_19100623","title":"IL-12 p40 homodimer, but not IL-12 p70, induces the expression of IL-16 in microglia and macrophages.","date":"2008","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19100623","citation_count":44,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28808017","id":"PMC_28808017","title":"Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages.","date":"2017","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/28808017","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7615703","id":"PMC_7615703","title":"Two markers, IS901-IS902 and p40, identified by PCR and by using monoclonal antibodies in Mycobacterium avium strains.","date":"1995","source":"Journal of clinical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/7615703","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9878528","id":"PMC_9878528","title":"LBP-p40 binds DNA tightly through associations with histones H2A, H2B, and H4.","date":"1998","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/9878528","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30580570","id":"PMC_30580570","title":"Deficiency of IL12p40 (Interleukin 12 p40) Promotes Ang II (Angiotensin II)-Induced Abdominal Aortic Aneurysm.","date":"2019","source":"Arteriosclerosis, thrombosis, and vascular biology","url":"https://pubmed.ncbi.nlm.nih.gov/30580570","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17559875","id":"PMC_17559875","title":"The crystal structure of the human Mov34 MPN domain reveals a metal-free dimer.","date":"2007","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17559875","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29073075","id":"PMC_29073075","title":"Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-γ.","date":"2017","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/29073075","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18367309","id":"PMC_18367309","title":"Interleukin-12 p40 gene (IL12B) polymorphisms and the risk of cervical cancer in Korean women.","date":"2008","source":"European journal of obstetrics, gynecology, and reproductive biology","url":"https://pubmed.ncbi.nlm.nih.gov/18367309","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15115313","id":"PMC_15115313","title":"The L1 retroelement-related p40 protein induces p38delta MAP kinase.","date":"2004","source":"Autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/15115313","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30235512","id":"PMC_30235512","title":"p40 Immunohistochemistry Is an Excellent Marker in Primary Lung Squamous Cell Carcinoma.","date":"2018","source":"Journal of pathology and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/30235512","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24152548","id":"PMC_24152548","title":"The central role of protein S12 in organizing the structure of the decoding site of the ribosome.","date":"2013","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/24152548","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22970855","id":"PMC_22970855","title":"Archaeal JAB1/MPN/MOV34 metalloenzyme (HvJAMM1) cleaves ubiquitin-like small archaeal modifier proteins (SAMPs) from protein-conjugates.","date":"2012","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22970855","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8954992","id":"PMC_8954992","title":"Analysis of nuclear localization of laminin binding protein precursor p40 (LBP/p40).","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8954992","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31342656","id":"PMC_31342656","title":"High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus.","date":"2020","source":"Arthritis & rheumatology (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/31342656","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21956105","id":"PMC_21956105","title":"Cooperation of p40(phox) with p47(phox) for Nox2-based NADPH oxidase activation during Fcγ receptor (FcγR)-mediated phagocytosis: mechanism for acquisition of p40(phox) phosphatidylinositol 3-phosphate (PI(3)P) binding.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21956105","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10456886","id":"PMC_10456886","title":"Role of Mycoplasma penetrans endonuclease P40 as a potential pathogenic determinant.","date":"1999","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/10456886","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3945556","id":"PMC_3945556","title":"The enigma of the gene coding for ribosomal protein S12 in the chloroplasts of Nicotiana.","date":"1986","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/3945556","citation_count":36,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30798982","id":"PMC_30798982","title":"Agreement of CK5/6, p40, and p63 immunoreactivity in non-small cell lung cancer.","date":"2019","source":"Pathology","url":"https://pubmed.ncbi.nlm.nih.gov/30798982","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25263848","id":"PMC_25263848","title":"p40 is a more specific marker than p63 for cutaneous poorly differentiated squamous cell carcinoma.","date":"2014","source":"Journal of cutaneous pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25263848","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3162077","id":"PMC_3162077","title":"Suppressors of temperature-sensitive mutations in a ribosomal protein gene, rpsL (S12), of Escherichia coli K12.","date":"1985","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/3162077","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8195128","id":"PMC_8195128","title":"The S12 ribosomal protein of Podospora anserina belongs to the S19 bacterial family and controls the mitochondrial genome integrity through cytoplasmic translation.","date":"1994","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8195128","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25263756","id":"PMC_25263756","title":"Expression of the p40 isoform of p63 has high specificity for cutaneous sarcomatoid squamous cell carcinoma.","date":"2014","source":"Journal of cutaneous pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25263756","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22930279","id":"PMC_22930279","title":"IL-20, IL-21 and p40: potential biomarkers of treatment response for ustekinumab.","date":"2013","source":"Acta dermato-venereologica","url":"https://pubmed.ncbi.nlm.nih.gov/22930279","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8985115","id":"PMC_8985115","title":"Identification of the active gene coding for the metastasis-associated 37LRP/p40 multifunctional protein.","date":"1996","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/8985115","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34512150","id":"PMC_34512150","title":"Deubiquitinase PSMD7 promotes the proliferation, invasion, and cisplatin resistance of gastric cancer cells by stabilizing RAD23B.","date":"2021","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34512150","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10200442","id":"PMC_10200442","title":"The induction of apoptosis in HeLa cells by the loss of LBP-p40.","date":"1998","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/10200442","citation_count":27,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21169565","id":"PMC_21169565","title":"A proteomic and transcriptomic approach reveals new insight into beta-methylthiolation of Escherichia coli ribosomal protein S12.","date":"2010","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/21169565","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18431321","id":"PMC_18431321","title":"Role of cytokine p40 family in multiple sclerosis.","date":"2008","source":"Minerva medica","url":"https://pubmed.ncbi.nlm.nih.gov/18431321","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38494478","id":"PMC_38494478","title":"Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation.","date":"2024","source":"Cell & bioscience","url":"https://pubmed.ncbi.nlm.nih.gov/38494478","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12237292","id":"PMC_12237292","title":"Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction and glucocorticoid-mediated signaling.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12237292","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29168459","id":"PMC_29168459","title":"p40 & thyroid transcription factor-1 immunohistochemistry: A useful panel to characterize non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS) category.","date":"2017","source":"The Indian journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/29168459","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11418654","id":"PMC_11418654","title":"Down-regulation of IL-12 p40 gene in Plasmodium berghei-infected mice.","date":"2001","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/11418654","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17512991","id":"PMC_17512991","title":"Modulation of 16S rRNA function by ribosomal protein S12.","date":"2007","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/17512991","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17578844","id":"PMC_17578844","title":"RIP2 mediates LPS-induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte-derived dendritic cells.","date":"2007","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/17578844","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25439327","id":"PMC_25439327","title":"Sigma receptor 1 activation attenuates release of inflammatory cytokines MIP1γ, MIP2, MIP3α, and IL12 (p40/p70) by retinal Müller glial cells.","date":"2015","source":"Journal of neurochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25439327","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"13679443","id":"PMC_13679443","title":"Regulation of interleukin 12 p40 and p70 production by blood and alveolar phagocytes during severe sepsis.","date":"2003","source":"Laboratory investigation; a journal of technical methods and pathology","url":"https://pubmed.ncbi.nlm.nih.gov/13679443","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19095621","id":"PMC_19095621","title":"A signal relay between ribosomal protein S12 and elongation factor EF-Tu during decoding of mRNA.","date":"2008","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/19095621","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25379961","id":"PMC_25379961","title":"Interplay of the bacterial ribosomal A-site, S12 protein mutations and paromomycin binding: a molecular dynamics study.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25379961","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29557072","id":"PMC_29557072","title":"Correlation between IL-17A/F, IL-23, IL-35 and IL-12/-23 (p40) levels in peripheral blood lymphocyte cultures and disease activity in Behcet's patients.","date":"2018","source":"Clinical rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/29557072","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11523260","id":"PMC_11523260","title":"A study on the expression of interleukin (IL)-10 and IL-12 P35, P40 mRNA in the psoriatic lesions.","date":"2001","source":"Journal of Tongji Medical University = Tong ji yi ke da xue xue bao","url":"https://pubmed.ncbi.nlm.nih.gov/11523260","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24993315","id":"PMC_24993315","title":"The utility of p63, p40, and GATA-binding protein 3 immunohistochemistry in diagnosing micropapillary urothelial carcinoma.","date":"2014","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/24993315","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29632807","id":"PMC_29632807","title":"PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal squamous cell carcinoma via the mTOR/p70S6K pathway.","date":"2018","source":"FEBS open bio","url":"https://pubmed.ncbi.nlm.nih.gov/29632807","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23021260","id":"PMC_23021260","title":"Identification of the major proteins of an immune modulating fraction from adult Fasciola hepatica released by Nonidet P40.","date":"2012","source":"Veterinary parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/23021260","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1279113","id":"PMC_1279113","title":"Nonintegrin laminin receptors in the nervous system: evidence for lack of a relationship to P40.","date":"1992","source":"Journal of neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/1279113","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32843061","id":"PMC_32843061","title":"A combination of cytokeratin 5/6, p63, p40 and MUC5AC are useful for distinguishing squamous cell carcinoma from adenocarcinoma of the cervix.","date":"2020","source":"Diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/32843061","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8811196","id":"PMC_8811196","title":"Structure and functions of the 20S and 26S proteasomes.","date":"1996","source":"Annual review of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8811196","citation_count":2108,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12167863","id":"PMC_12167863","title":"Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein.","date":"2002","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12167863","citation_count":1924,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16169070","id":"PMC_16169070","title":"A human protein-protein interaction network: a resource for annotating the proteome.","date":"2005","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/16169070","citation_count":1704,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12477932","id":"PMC_12477932","title":"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12477932","citation_count":1479,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19489727","id":"PMC_19489727","title":"Recognition and processing of ubiquitin-protein conjugates by the proteasome.","date":"2009","source":"Annual review of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19489727","citation_count":1398,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19615732","id":"PMC_19615732","title":"Defining the human deubiquitinating enzyme interaction landscape.","date":"2009","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/19615732","citation_count":1282,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12808466","id":"PMC_12808466","title":"Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts.","date":"2003","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12808466","citation_count":1236,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12809610","id":"PMC_12809610","title":"DNA deamination mediates innate immunity to retroviral infection.","date":"2003","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/12809610","citation_count":1150,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26186194","id":"PMC_26186194","title":"The BioPlex Network: A Systematic Exploration of the Human Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26496610","id":"PMC_26496610","title":"A human interactome in three quantitative dimensions organized by stoichiometries and abundances.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26496610","citation_count":1015,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14564014","id":"PMC_14564014","title":"Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex.","date":"2003","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/14564014","citation_count":1006,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25416956","id":"PMC_25416956","title":"A proteome-scale map of the human interactome network.","date":"2014","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/25416956","citation_count":977,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12808465","id":"PMC_12808465","title":"The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA.","date":"2003","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12808465","citation_count":912,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23503661","id":"PMC_23503661","title":"Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.","date":"2013","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/23503661","citation_count":870,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32296183","id":"PMC_32296183","title":"A reference map of the human binary protein interactome.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32296183","citation_count":849,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14743216","id":"PMC_14743216","title":"A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.","date":"2004","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/14743216","citation_count":841,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29507755","id":"PMC_29507755","title":"VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.","date":"2018","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/29507755","citation_count":829,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14528300","id":"PMC_14528300","title":"The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif.","date":"2003","source":"Nature medicine","url":"https://pubmed.ncbi.nlm.nih.gov/14528300","citation_count":798,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12859895","id":"PMC_12859895","title":"Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif.","date":"2003","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/12859895","citation_count":763,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14702039","id":"PMC_14702039","title":"Complete sequencing and characterization of 21,243 full-length human cDNAs.","date":"2003","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/14702039","citation_count":754,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"17353931","id":"PMC_17353931","title":"Large-scale mapping of human protein-protein interactions by mass spectrometry.","date":"2007","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/17353931","citation_count":733,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33961781","id":"PMC_33961781","title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33961781","citation_count":705,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22939629","id":"PMC_22939629","title":"A census of human soluble protein complexes.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22939629","citation_count":689,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14528301","id":"PMC_14528301","title":"HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation.","date":"2003","source":"Nature medicine","url":"https://pubmed.ncbi.nlm.nih.gov/14528301","citation_count":679,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21873635","id":"PMC_21873635","title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.","date":"2011","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/21873635","citation_count":656,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14527406","id":"PMC_14527406","title":"HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability.","date":"2003","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/14527406","citation_count":607,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22190034","id":"PMC_22190034","title":"Global landscape of HIV-human protein complexes.","date":"2011","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/22190034","citation_count":593,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29395067","id":"PMC_29395067","title":"High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies.","date":"2018","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/29395067","citation_count":580,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12750511","id":"PMC_12750511","title":"Hypermutation of HIV-1 DNA in the absence of the Vif protein.","date":"2003","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/12750511","citation_count":570,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":50606,"output_tokens":2310,"usd":0.093234},"stage2":{"model":"claude-opus-4-6","input_tokens":5622,"output_tokens":2484,"usd":0.135315},"total_usd":0.483164,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":61739,"output_tokens":3898,"usd":0.121843},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":6693,"output_tokens":2202,"usd":0.132772}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"The MPN domain of human PSMD7/Mov34 adopts a metalloprotease fold but is unable to coordinate a zinc ion, explaining its lack of catalytic isopeptidase/deubiquitylase activity; the MPN domain functions primarily as a structural scaffold rather than a catalytic enzyme.\",\n      \"method\": \"Crystal structure of C-terminally truncated MPN domain solved to 1.96 Å and 3.0 Å, combined with size-exclusion chromatography and DLS showing a domain-swapped dimer in solution; comparison with zinc-binding archaeal AfJAMM structure and amino acid sequence analysis\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure with functional validation by biophysical methods and sequence analysis; single rigorous paper\",\n      \"pmids\": [\"17559875\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PSMD7 (Rpn8 ortholog) forms a heterodimer with the catalytic deubiquitinase Rpn11 (PSMD14) via two distinct interfaces within their MPN domains; this heterodimer is required for proper deubiquitinase activity and substrate deubiquitination at the proteasome.\",\n      \"method\": \"2.0-Å crystal structure of Saccharomyces cerevisiae Rpn11–Rpn8 heterodimer (Zn2+-free and Zn2+-bound forms), combined with mutational analysis of interface residues and in vitro deubiquitinase assays\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure plus mutagenesis plus in vitro enzymatic assay; replicated by independent structural study same year\",\n      \"pmids\": [\"24463465\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The Rpn11–Rpn8 (PSMD14–PSMD7) MPN heterodimer exhibits deubiquitylation activity toward a model substrate that requires incorporation into the 26S proteasome and ATP hydrolysis for full activation, indicating coupling of substrate unfolding/translocation to ubiquitin removal.\",\n      \"method\": \"Crystal structures of Rpn8–Rpn11 fusion protein in complex with a nanobody (three structures), in vitro deubiquitylation assay, docking into proteasome EM density\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure, in vitro enzymatic assay, and EM docking; independent of the Worden et al. study\",\n      \"pmids\": [\"24516147\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"PSMD7 (hVIP/MOV34) interacts directly with HIV-1 Vpr protein in vitro and in vivo; this interaction causes relocalization of hVIP/MOV34 from the nucleus to a perinuclear distribution and is associated with Vpr-induced G2/M cell cycle arrest and inhibition of maturation-promoting factor (histone H1 kinase) activity.\",\n      \"method\": \"Yeast two-hybrid cloning, in vitro binding assay, co-immunoprecipitation in mammalian cells, immunofluorescence localization, histone H1 kinase activity assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction shown in vitro and in vivo with functional readout (kinase activity, localization change); single laboratory\",\n      \"pmids\": [\"9520381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The carboxyl-terminal domain of PSMD7 (hVIP/MOV34) is required for its interaction with HIV-1 Vpr and for dexamethasone/glucocorticoid-induced nuclear translocation, indicating PSMD7 participates in glucocorticoid receptor signaling and nucleocytoplasmic shuttling.\",\n      \"method\": \"Deletion mutagenesis panel of hVIP, co-immunoprecipitation, immunofluorescence localization with glucocorticoid agonist/antagonist treatment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — domain mapping by deletion mutagenesis with functional localization readout; single laboratory\",\n      \"pmids\": [\"12237292\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"PSMD7 (p28/p40.5, human Nas7p homologue) was identified as a novel non-ATPase subunit of the PA700 (19S regulatory complex) of the 26S proteasome; its yeast homologue NAS7 disruption causes heat-stress sensitivity, indicating a role in proteasome function under stress.\",\n      \"method\": \"cDNA cloning, sequence homology analysis, yeast gene disruption with viability and heat-stress phenotyping\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — biochemical identification of subunit plus genetic loss-of-function phenotype in yeast ortholog\",\n      \"pmids\": [\"9714768\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMD7 acts as a deubiquitinase that stabilizes RAD23B protein by preventing its ubiquitin-mediated degradation; PSMD7 physically interacts with RAD23B, and PSMD7 knockdown increases RAD23B ubiquitination and reduces RAD23B and XPC protein levels in gastric cancer cells, promoting cisplatin sensitivity.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, protein overexpression, xenograft mouse model\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP plus ubiquitination assay plus in vivo model; single laboratory\",\n      \"pmids\": [\"34512150\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PSMD7 knockdown in esophageal squamous cell carcinoma cells reduces proteasomal function, decreases proliferation, increases apoptosis, and suppresses the mTOR/p70S6K signaling pathway; conversely, PSMD7 overexpression activates p-mTOR and p-p70S6K, placing PSMD7 upstream of mTOR/p70S6K in a pro-survival signaling axis.\",\n      \"method\": \"Lentiviral shRNA knockdown, PSMD7 overexpression, western blotting for pathway components, proteasome activity assay, xenograft tumor model\",\n      \"journal\": \"FEBS open bio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss- and gain-of-function with pathway readout and in vivo validation; single laboratory\",\n      \"pmids\": [\"29632807\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PSMD7 deubiquitinates and stabilizes SOX2 protein in pancreatic cancer cells, thereby activating the Notch1 signaling pathway and promoting cancer cell progression; restoration of SOX2 rescues the anti-tumor effects of PSMD7 silencing.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, shRNA and overexpression in vitro and in vivo, epistasis rescue experiment with SOX2 re-expression\",\n      \"journal\": \"Cell & bioscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP, ubiquitination assay, genetic epistasis; single laboratory\",\n      \"pmids\": [\"38494478\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PSMD7 (Mov34/hVIP) is a non-catalytic MPN-domain subunit of the 19S proteasome regulatory particle that heterodimerizes with the catalytic deubiquitinase PSMD14 (Rpn11); although its MPN domain adopts a metalloprotease fold it cannot coordinate zinc and lacks intrinsic isopeptidase activity, instead serving a structural role that supports PSMD14-dependent co-translocational deubiquitination of proteasome substrates, while also functioning as a deubiquitinase that stabilizes specific substrates (RAD23B, SOX2) to regulate proteasomal degradation, mTOR/p70S6K signaling, and cell survival.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll systematically classify each paper before extracting discoveries.\n\n**Classification of key papers:**\n\n- Papers [1]-[15], [17]-[35], [37]-[60], [62]-[79], [81]-[83], [85]-[96], [98]-[100] (retrieved): These describe IL-12 p40, p63/p40 isoform, ribosomal S12, Lactobacillus p40, phagocyte p40(phox), eIF3-p40, LINE-1 p40, laminin receptor p40, etc. — all are ALIAS COLLISIONS with \"p40\" or \"p12/S12\" symbols. EXCLUDE.\n\n- Paper [16] (retrieved, PMID:24463465): Rpn11-Rpn8 structure — describes yeast Rpn11 (PSMD14 ortholog) and Rpn8 (PSMD7 ortholog). KEEP as ortholog study relevant to the MPN domain heterodimer.\n\n- Paper [19] (retrieved, PMID:24516147): Rpn8-Rpn11 crystal structure — same complex, Rpn8 is PSMD7 ortholog. KEEP.\n\n- Paper [30] (retrieved, PMID:9520381): hVIP/MOV34 interacts with HIV-1 Vpr — MOV34/hVIP is PSMD7. KEEP.\n\n- Paper [36] (retrieved, PMID:9714768): p40.5 (Nas7p) cDNA cloning — describes p40.5 as PSMD7 homolog (human p40.5 = Nas7p). KEEP.\n\n- Paper [61] (retrieved, PMID:17559875): Crystal structure of human Mov34 MPN domain — directly about PSMD7/Mov34. KEEP.\n\n- Paper [80] (retrieved, PMID:34512150): PSMD7 in gastric cancer, stabilizes RAD23B. KEEP.\n\n- Paper [84] (retrieved, PMID:38494478): PSMD7 in pancreatic cancer, stabilizes SOX2. KEEP.\n\n- Paper [85] (retrieved, PMID:12237292): hVIP/mov34 carboxyl terminus and Vpr interaction — hVIP is PSMD7. KEEP.\n\n- Paper [97] (retrieved, PMID:29632807): PSMD7 in esophageal cancer, mTOR/p70S6K pathway. KEEP.\n\n**Curated papers:**\n- [1] PMID:8811196: 26S proteasome structure/functions — general review, mentions 19S subunits including non-ATPases. KEEP (provides context for PSMD7 as 19S non-ATPase subunit).\n- [5] PMID:19489727: Proteasome recognition/processing — mentions Rpn8/Rpn11 DUB pair. KEEP.\n- [6] PMID:19615732: DUB interaction landscape — PSMD7 interactions mapped. KEEP.\n- Others in curated list describe APOBEC3G/Vif, interactomes — the interactome papers may incidentally list PSMD7 but provide no specific mechanistic findings. EXCLUDE from discoveries unless specific.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"PSMD7 (hVIP/MOV34), a 34-kDa member of the MOV34 family and component of the 26S proteasome 19S regulatory complex, was identified as a direct binding partner of HIV-1 Vpr by yeast two-hybrid assay and confirmed by in vitro and in vivo co-immunoprecipitation. hVIP/MOV34 localizes to the nucleus and its subcellular localization shifts from nuclear to perinuclear upon Vpr-induced G2/M cell-cycle arrest, coinciding with inhibition of MPF-associated histone H1 kinase activity, indicating a functional role in cell-cycle regulation.\",\n      \"method\": \"Yeast two-hybrid, in vitro binding assay, in vivo co-immunoprecipitation, immunofluorescence localization, histone H1 kinase activity assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — reciprocal binding confirmed in vitro and in vivo, localization tied to functional phenotype, but single lab\",\n      \"pmids\": [\"9520381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Human PSMD7 (p40.5) was cloned and identified as a non-ATPase subunit of the PA700 (19S) regulatory complex of the 26S proteasome, homologous to yeast Nas7p. Disruption of the yeast NAS7 gene caused hypersensitivity to heat stress (inability to grow at 37°C), while NAS6 disruption had no effect, demonstrating that Nas7p/PSMD7 is required for normal proteasome function under stress conditions.\",\n      \"method\": \"cDNA cloning, sequence homology analysis, yeast gene disruption with phenotypic readout (heat-stress sensitivity)\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function in yeast ortholog with defined phenotype; single study\",\n      \"pmids\": [\"9714768\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The carboxyl-terminal domain of hVIP/MOV34 (PSMD7) is critical for its interaction with HIV-1 Vpr, as C-terminal deletion mutants abolish both Vpr binding and Vpr-induced nuclear relocalization of hVIP. Full-length hVIP is cytoplasmic but translocates to the nucleus in the presence of Vpr or dexamethasone; C-terminal mutants are unresponsive to both Vpr and glucocorticoids, linking PSMD7's C-terminus to glucocorticoid receptor signaling.\",\n      \"method\": \"Deletion mutagenesis, co-immunoprecipitation, immunofluorescence localization, pharmacological manipulation (dexamethasone/glucocorticoid antagonist)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — domain mapping with mutagenesis and functional localization readout; single lab\",\n      \"pmids\": [\"12237292\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The crystal structure of the MPN domain of human PSMD7 (Mov34) was solved at 1.96 Å resolution and revealed a nine-β-strand/three-α-helix fold with a domain-swap dimer in solution. Unlike the catalytically active JAMM/MPN+ domains of Rpn11 (PSMD14) and Csn5, the PSMD7 MPN domain lacks the zinc-coordinating residues required for metalloprotease activity (the JAMM motif is degenerate), explaining why PSMD7 has no isopeptidase activity and instead serves a structural role within the 19S proteasome lid.\",\n      \"method\": \"X-ray crystallography (1.96 Å and 3.0 Å), size-exclusion chromatography, dynamic light scattering, amino acid sequence comparison\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — high-resolution crystal structure with biophysical validation and functional inference from active-site analysis\",\n      \"pmids\": [\"17559875\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Crystal structures of the yeast Rpn8-Rpn11 MPN-domain heterodimer (the ortholog of human PSMD7-PSMD14) at 2.0 Å revealed that Rpn8 (PSMD7 ortholog) forms two distinct interfaces with the catalytically active Rpn11 (PSMD14 ortholog). Rpn8 is required to stabilize Rpn11 in the heterodimer; structural and mutational analysis showed that Rpn11 lacks a conserved surface for ubiquitin Ile44-patch binding and exhibits no linkage specificity, functioning as a promiscuous deubiquitinase for co-translocation substrate deubiquitination.\",\n      \"method\": \"X-ray crystallography (2.0 Å), in vitro deubiquitinase activity assay, site-directed mutagenesis\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — high-resolution structure combined with in vitro enzymatic assay and mutagenesis in a single rigorous study\",\n      \"pmids\": [\"24463465\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Crystal structures of the Rpn8-Rpn11 heterodimer (human PSMD7-PSMD14 orthologs) showed that full DUB activation of Rpn11 requires its incorporation into the 26S proteasome and is dependent on ATP hydrolysis, suggesting coupling of substrate processing with ubiquitin removal. An insertion segment in Rpn11 acts as a physical barrier across the substrate access channel and a conformationally unstable catalytic loop prevent premature deubiquitination; contacts with ATPase subunits (observed by docking into EM density) stabilize the active conformation. Rpn8 (PSMD7) contributes structurally to forming the active heterodimer.\",\n      \"method\": \"X-ray crystallography, nanobody-assisted crystallization, in vitro DUB activity assay, EM density docking\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — multiple orthogonal structural and biochemical methods; independently replicates Rpn8-Rpn11 heterodimer findings from companion paper\",\n      \"pmids\": [\"24516147\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Global proteomic analysis of deubiquitinase-associated complexes confirmed that PSMD7 (as part of the 19S proteasome lid) is a component of the deubiquitinase interaction landscape, associating with the 26S proteasome complex including PSMD14 and other 19S regulatory particle subunits.\",\n      \"method\": \"Affinity purification–mass spectrometry (AP-MS) with CompPASS scoring\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — large-scale AP-MS with computational confidence scoring; confirms complex membership but not mechanistic detail specific to PSMD7\",\n      \"pmids\": [\"19615732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PSMD7 knockdown in esophageal squamous cell carcinoma (EC9706) cells decreased proliferation, increased apoptosis, reduced proteasomal function, and suppressed mTOR/p70S6K pathway activity (lower p-mTOR Ser2448 and p-p70S6K Thr421/Ser424). Conversely, PSMD7 overexpression in Het-1A cells increased phosphorylation of mTOR and p70S6K, placing PSMD7 upstream of mTOR/p70S6K signaling. In vivo xenograft experiments confirmed decelerated tumor growth upon PSMD7 knockdown with attenuated mTOR/p70S6K signaling.\",\n      \"method\": \"Lentivirus-mediated shRNA knockdown, overexpression, Western blotting for pathway components, cell proliferation/apoptosis assays, in vivo xenograft\",\n      \"journal\": \"FEBS open bio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — loss- and gain-of-function with defined molecular readout; single lab, pathway placement via phospho-protein analysis\",\n      \"pmids\": [\"29632807\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMD7 functions as a deubiquitinase in gastric cancer cells, directly interacting with RAD23B (confirmed by co-immunoprecipitation) and stabilizing RAD23B protein by preventing its ubiquitin-mediated proteasomal degradation. PSMD7 knockdown enhanced RAD23B ubiquitination and degradation, reduced XPC protein levels (a RAD23B-dependent DNA repair factor), suppressed proliferation/invasion, increased cisplatin sensitivity, and inhibited tumor growth in vivo, defining the PSMD7–RAD23B–XPC axis as a mechanism of chemotherapy resistance.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, overexpression, cell viability/apoptosis/DNA damage repair assays, in vivo xenograft\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP confirms binding, ubiquitination assay establishes DUB substrate relationship, multiple functional readouts; single lab\",\n      \"pmids\": [\"34512150\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PSMD7 deubiquitinates and stabilizes SOX2 protein in pancreatic cancer cells, preventing its proteasomal degradation. Stabilized SOX2 activates the Notch1 signaling pathway, promoting pancreatic cancer cell proliferation and invasion. Restoration of SOX2 expression rescued the antitumor effect of PSMD7 silencing, placing PSMD7 upstream of SOX2–Notch1 in pancreatic cancer progression.\",\n      \"method\": \"In vitro and in vivo gain/loss-of-function assays, co-immunoprecipitation, ubiquitination assay, rescue experiments with SOX2 re-expression, Notch1 pathway reporter analysis\",\n      \"journal\": \"Cell & bioscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — epistasis via rescue experiment, Co-IP and ubiquitination assay define DUB-substrate relationship; single lab\",\n      \"pmids\": [\"38494478\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PSMD7 (Mov34/hVIP) is a non-catalytic MPN-domain subunit of the 26S proteasome 19S regulatory lid that forms an obligate structural heterodimer with the active deubiquitinase PSMD14 (Rpn11); PSMD7's degenerate JAMM motif renders it catalytically inactive for isopeptide-bond cleavage, but it stabilizes and activates PSMD14 within the lid complex, and in cancer contexts PSMD7 itself exhibits deubiquitinase activity toward substrates RAD23B and SOX2, stabilizing them to promote proliferation, chemoresistance, and Notch1 signaling, while also interacting with HIV-1 Vpr to modulate cell-cycle progression.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PSMD7 is a non-catalytic MPN-domain subunit of the 19S regulatory particle of the 26S proteasome that functions as an essential structural partner of the deubiquitinase PSMD14 (Rpn11), forming a heterodimer required for co-translocational deubiquitination of proteasome substrates [PMID:24463465, PMID:24516147]. Its MPN domain adopts a metalloprotease fold but cannot coordinate zinc and therefore lacks intrinsic isopeptidase activity, serving instead as a scaffold [PMID:17559875]. Beyond its structural role in the proteasome, PSMD7 stabilizes specific proteins—including RAD23B and SOX2—by opposing their ubiquitin-mediated degradation, thereby influencing DNA repair, Notch1 signaling, and mTOR/p70S6K pro-survival signaling [PMID:34512150, PMID:38494478, PMID:29632807]. PSMD7 also interacts with HIV-1 Vpr, and this interaction contributes to Vpr-induced G2/M cell cycle arrest [PMID:9520381].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Identification of PSMD7 as a bona fide non-ATPase subunit of the 19S proteasome established its position within the ubiquitin-proteasome system and showed that its yeast ortholog is important for stress-dependent proteasome function.\",\n      \"evidence\": \"cDNA cloning, sequence homology, and yeast NAS7 gene disruption with heat-stress phenotyping\",\n      \"pmids\": [\"9714768\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which loss of PSMD7/Nas7 causes heat sensitivity was not defined\",\n        \"No biochemical activity was attributed to the protein\"\n      ]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Discovery that HIV-1 Vpr binds PSMD7 and relocalizes it from the nucleus to a perinuclear compartment linked a proteasome subunit to viral pathogenesis and G2/M arrest for the first time.\",\n      \"evidence\": \"Yeast two-hybrid, in vitro binding, co-immunoprecipitation, immunofluorescence, histone H1 kinase assay in mammalian cells\",\n      \"pmids\": [\"9520381\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the Vpr–PSMD7 interaction is direct or bridged by other proteasome subunits in vivo was not resolved\",\n        \"Mechanism connecting PSMD7 relocalization to MPF inhibition was not elucidated\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Mapping the Vpr-binding and glucocorticoid-responsive nuclear translocation determinants to the C-terminal domain of PSMD7 revealed domain-specific functions beyond proteasome assembly.\",\n      \"evidence\": \"Deletion mutagenesis, co-immunoprecipitation, immunofluorescence with glucocorticoid agonist/antagonist in mammalian cells\",\n      \"pmids\": [\"12237292\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Role of PSMD7 in glucocorticoid receptor signaling was correlative; no direct mechanistic link to transcription was shown\",\n        \"Single laboratory finding\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Solving the crystal structure of the PSMD7 MPN domain explained why this subunit lacks deubiquitinase activity—it adopts a metalloprotease fold but cannot coordinate zinc—establishing its identity as a catalytically inactive MPN (MPN−) scaffold.\",\n      \"evidence\": \"Crystal structures at 1.96 Å and 3.0 Å resolution, size-exclusion chromatography, dynamic light scattering, comparison with zinc-binding AfJAMM\",\n      \"pmids\": [\"17559875\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure lacked the C-terminal tail important for proteasome integration and Vpr binding\",\n        \"No partner co-structure was available to show how the MPN domain interfaces with PSMD14\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Two independent crystal structures of the PSMD14–PSMD7 (Rpn11–Rpn8) heterodimer demonstrated that PSMD7 forms an obligate dimer with the catalytic deubiquitinase PSMD14 via dual MPN-domain interfaces and that this heterodimerization is required for deubiquitination activity, which in turn is fully activated only upon proteasome incorporation and ATP hydrolysis.\",\n      \"evidence\": \"Crystal structures of yeast Rpn11–Rpn8 heterodimer (Zn-free and Zn-bound), Rpn8–Rpn11 fusion with nanobody, mutational analysis, in vitro DUB assays, EM docking\",\n      \"pmids\": [\"24463465\", \"24516147\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"High-resolution human PSMD7–PSMD14 structure was not reported\",\n        \"Contribution of PSMD7 to substrate engagement or lid conformational changes was not dissected\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Loss- and gain-of-function experiments linked PSMD7 to cell proliferation, apoptosis, and mTOR/p70S6K signaling in cancer cells, demonstrating that its proteasomal role has downstream consequences for growth-regulatory pathways.\",\n      \"evidence\": \"Lentiviral shRNA knockdown, overexpression, western blotting, proteasome activity assay, xenograft model in esophageal squamous cell carcinoma\",\n      \"pmids\": [\"29632807\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific proteasome substrate(s) whose stabilization or degradation controls mTOR/p70S6K was not identified\",\n        \"Single laboratory and single cancer type\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identification of RAD23B as a direct PSMD7-interacting protein whose ubiquitination and degradation are opposed by PSMD7 connected the subunit to nucleotide excision repair capacity and cisplatin sensitivity.\",\n      \"evidence\": \"Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, protein overexpression, gastric cancer xenograft model\",\n      \"pmids\": [\"34512150\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether PSMD7 deubiquitinates RAD23B directly or recruits another DUB was not distinguished\",\n        \"Generalizability beyond gastric cancer not tested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"PSMD7 was shown to deubiquitinate and stabilize SOX2, activating Notch1 signaling in pancreatic cancer, broadening the repertoire of substrates whose stability PSMD7 controls beyond the canonical proteasome degradation role.\",\n      \"evidence\": \"Co-immunoprecipitation, ubiquitination assay, shRNA/overexpression, epistasis rescue with SOX2 re-expression in pancreatic cancer cells and xenografts\",\n      \"pmids\": [\"38494478\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the reported deubiquitinase activity resides intrinsically in PSMD7 or is mediated through PSMD14 within the proteasome remains unresolved\",\n        \"No in vitro reconstitution with purified components was performed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A central unresolved question is whether PSMD7 possesses any intrinsic deubiquitinase activity or whether the substrate-stabilizing effects attributed to it (RAD23B, SOX2) are indirect consequences of modulating PSMD14 activity or proteasome function.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro reconstitution with purified recombinant PSMD7 alone has demonstrated direct DUB activity\",\n        \"Structural basis for how PSMD7 selectively protects specific substrates from degradation is unknown\",\n        \"Whether PSMD7 functions outside the assembled 26S proteasome has not been established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 2, 6, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1, 2, 5, 7]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [7, 8]}\n    ],\n    \"complexes\": [\n      \"26S proteasome 19S regulatory particle\",\n      \"PSMD14-PSMD7 MPN heterodimer\"\n    ],\n    \"partners\": [\n      \"PSMD14\",\n      \"RAD23B\",\n      \"SOX2\",\n      \"HIV-1 Vpr\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"PSMD7 is a non-catalytic MPN-domain subunit of the 26S proteasome 19S regulatory particle lid that forms an obligate heterodimer with the deubiquitinase PSMD14 (Rpn11), stabilizing and activating PSMD14's isopeptidase function during substrate translocation [PMID:24463465, PMID:24516147]. The PSMD7 MPN domain contains a degenerate JAMM motif lacking zinc-coordinating residues essential for metalloprotease activity, rendering it catalytically inactive as an isopeptidase and assigning it a primarily structural role within the lid [PMID:17559875]. Its yeast ortholog Nas7p is required for proteasome function under stress [PMID:9714768], and PSMD7 interacts with HIV-1 Vpr through its C-terminal domain, linking it to Vpr-induced G2/M arrest [PMID:9520381, PMID:12237292]. In cancer contexts, PSMD7 has been reported to deubiquitinate and stabilize RAD23B and SOX2, promoting chemoresistance via the RAD23B–XPC DNA-repair axis and activating Notch1 signaling through SOX2, respectively [PMID:34512150, PMID:38494478].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Identification of PSMD7 as a 26S proteasome 19S regulatory subunit and HIV-1 Vpr interactor established its dual role in proteasome biology and viral exploitation of the cell cycle.\",\n      \"evidence\": \"Yeast two-hybrid, co-immunoprecipitation, yeast NAS7 gene disruption with heat-stress phenotype\",\n      \"pmids\": [\"9520381\", \"9714768\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which Vpr–PSMD7 interaction triggers G2/M arrest not defined\", \"Whether PSMD7 has proteasome-independent functions in cell-cycle control unclear\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Mapping the Vpr-binding determinant to PSMD7's C-terminal domain and linking this region to glucocorticoid receptor–mediated nuclear import revealed a domain-specific mechanism for PSMD7 relocalization.\",\n      \"evidence\": \"Deletion mutagenesis, co-immunoprecipitation, immunofluorescence with dexamethasone and glucocorticoid antagonist treatments\",\n      \"pmids\": [\"12237292\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct binding between PSMD7 C-terminus and glucocorticoid receptor shown\", \"Functional consequence of nuclear relocalization on proteasome activity not tested\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"The crystal structure of the PSMD7 MPN domain resolved why it lacks isopeptidase activity: its degenerate JAMM motif cannot coordinate the catalytic zinc ion, establishing PSMD7 as a structural rather than enzymatic MPN subunit.\",\n      \"evidence\": \"X-ray crystallography at 1.96 Å, size-exclusion chromatography, sequence comparison with catalytically active JAMM domains\",\n      \"pmids\": [\"17559875\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure of full-length PSMD7 not determined\", \"Contribution of non-MPN regions to proteasome lid assembly unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"High-resolution structures of the PSMD7–PSMD14 (Rpn8–Rpn11) heterodimer demonstrated that PSMD7 is an obligate activating partner of PSMD14, and that full deubiquitinase activation requires incorporation into the 26S proteasome and is coupled to ATP hydrolysis.\",\n      \"evidence\": \"X-ray crystallography at 2.0 Å, in vitro DUB activity assays, site-directed mutagenesis, EM density docking (two independent studies)\",\n      \"pmids\": [\"24463465\", \"24516147\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Conformational dynamics of the insertion-loop gating mechanism not resolved at atomic level in the intact 26S context\", \"Contribution of individual PSMD7–PSMD14 interfaces to lid assembly versus DUB activation not dissected\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Functional studies in esophageal cancer showed PSMD7 knockdown impairs proteasome function and suppresses mTOR/p70S6K signaling, linking proteasome subunit stoichiometry to growth-factor pathway output.\",\n      \"evidence\": \"Lentiviral shRNA knockdown and overexpression, phospho-Western blotting, in vivo xenograft\",\n      \"pmids\": [\"29632807\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether mTOR/p70S6K effects are specific to PSMD7 or secondary to general proteasome impairment not distinguished\", \"No proteasome activity quantification beyond pathway phospho-readouts\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Discovery that PSMD7 directly deubiquitinates and stabilizes RAD23B, thereby maintaining XPC-dependent DNA repair and conferring cisplatin resistance, revealed an unexpected substrate-directed DUB function for a supposedly catalytically inactive MPN subunit.\",\n      \"evidence\": \"Co-immunoprecipitation, in vivo ubiquitination assay, shRNA knockdown/overexpression, cisplatin sensitivity assays, xenograft\",\n      \"pmids\": [\"34512150\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct isopeptidase activity of PSMD7 on RAD23B not reconstituted with purified recombinant protein\", \"Whether DUB activity is intrinsic to PSMD7 or mediated through co-purifying PSMD14 not excluded\", \"Not independently replicated\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extension of the DUB paradigm to SOX2 in pancreatic cancer, with epistasis rescue experiments placing PSMD7 upstream of SOX2–Notch1 signaling, broadened the substrate repertoire attributed to PSMD7.\",\n      \"evidence\": \"Co-immunoprecipitation, ubiquitination assay, SOX2 rescue experiments, Notch1 pathway reporter assays, in vivo xenograft\",\n      \"pmids\": [\"38494478\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vitro reconstitution of PSMD7-catalyzed SOX2 deubiquitination not performed\", \"Catalytic residues responsible for DUB activity not identified given the degenerate JAMM motif\", \"Whether PSMD14 co-purifies in cancer-context immunoprecipitates not controlled\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The central unresolved question is whether the reported DUB activity toward RAD23B and SOX2 is intrinsic to PSMD7 or mediated by co-purifying PSMD14, given that structural data show PSMD7 lacks the canonical catalytic zinc site.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reconstitution of purified recombinant PSMD7 DUB activity in vitro is needed\", \"Catalytic-site mutagenesis in PSMD7 to abolish reported DUB activity not performed\", \"Proteasome-independent versus proteasome-dependent roles of PSMD7 in cancer not delineated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [3, 4, 5]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [8, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [3, 4, 5, 6]}\n    ],\n    \"complexes\": [\n      \"26S proteasome 19S regulatory particle (lid)\"\n    ],\n    \"partners\": [\n      \"PSMD14\",\n      \"RAD23B\",\n      \"SOX2\",\n      \"HIV-1 Vpr\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}