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Showing PSMC5 — RPT6 is a alias.

PSMC5

26S proteasome regulatory subunit 8 · UniProt P62195

Length
406 aa
Mass
45.6 kDa
Annotated
2026-06-10
55 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMC5 (SUG1/TRIP1/RPT6) is an essential AAA+ ATPase subunit of the 19S regulatory particle of the 26S proteasome that couples ATP-dependent protein degradation to the control of transcription, signaling, and cell fate (PMID:8628401, PMID:8710853). Beyond its structural role in the proteasome, recombinant PSMC5 has intrinsic Mg2+-dependent ATPase activity that is stimulated specifically by poly(U)/poly(C) and poly(A)+ mRNA, and an ATP-binding-domain-dependent 3'→5' DNA helicase activity (PMID:9054406, PMID:9287326). A recurrent theme is that PSMC5 docks onto the activation domains of transcription factors and nuclear receptors to couple their proteasomal turnover with transactivation: it binds the AF-2 domains of VDR and RARs and the coactivator SRC-3 in a ligand-dependent manner, and stimulates proteasome-dependent degradation of Sp1, with ATP hydrolysis required and ATPase-dead mutants acting as dominant negatives (PMID:9831079, PMID:10816420, PMID:12110588, PMID:19144644). In the immune system, PSMC5 associates with the MHC class II transactivator CIITA and is recruited to MHC class I and II promoters, where it binds acetylated histone H3 and recruits the acetyltransferase CBP to drive promoter H3 acetylation and transcription (PMID:18215421, PMID:18662994, PMID:22771340). PSMC5 also remodels signaling scaffolds and ubiquitination: it relocalizes the Shoc2–RAF-1 complex to endosomes and displaces the E3 ligase HUWE1 (PMID:26519477), engages NLRC4/Ipaf to promote caspase-8-dependent cell death (PMID:20085538, PMID:27974463), and drives SMURF1-dependent K11-ubiquitination of METTL14 to remodel m6A and promote tumor growth (PMID:42212325). Loss-of-function mutations, including P320R and haploinsufficiency, weaken 19S–20S proteasome association and impair proteasome function, causing neurodevelopmental proteasomopathies characterized by protein aggregation, mitochondrial dysfunction, integrated-stress-response activation, and immune dysregulation (PMID:38776958, PMID:41298377).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 High

    Resolved whether Sug1 belongs to the transcription machinery or the proteasome, establishing PSMC5 as a 26S proteasome subunit required for ubiquitin-dependent proteolysis.

    Evidence Biochemical co-purification and functional proteolysis assays in yeast mutants; nuclear fractionation, reciprocal Co-IP and antibody depletion in mammalian cells

    PMID:8628401 PMID:8710853

    Open questions at the time
    • Did not define which substrates require Sug1 specifically
    • Structural position within the 19S particle not resolved
  2. 1997 High

    Defined PSMC5's intrinsic enzymatic activities—ATP-domain-dependent DNA helicase and RNA-stimulated ATPase—indicating activities beyond simple unfoldase function.

    Evidence In vitro helicase and ATPase assays with recombinant protein, ATPase-domain mutagenesis, UV cross-linking, RNA-stimulation panels

    PMID:9054406 PMID:9287326

    Open questions at the time
    • Physiological relevance of helicase and RNA-stimulated ATPase activities in the assembled proteasome not established
    • No cellular substrate of the helicase activity identified
  3. 1997 Medium

    Linked PSMC5 to transcription/repair machinery via XPB/TFIIH, hinting at a role coupling proteolysis to transcription.

    Evidence Yeast two-hybrid, baculovirus co-expression, co-purification with TFIIH, in vivo overexpression phenotype

    PMID:9173976

    Open questions at the time
    • Functional consequence of TFIIH association not separated from general proteasome effects
    • Single lab
  4. 1998 High

    Established the paradigm that PSMC5 couples ligand-dependent nuclear receptor degradation to transactivation, using VDR as the first example.

    Evidence Co-IP, transient overexpression, proteasome inhibitors, ATPase-dead K196H mutant, reporter assays, cycloheximide chase

    PMID:9831079

    Open questions at the time
    • Whether degradation is required for activation or a parallel event not fully resolved
    • Generality beyond VDR untested at this stage
  5. 1998 Medium

    Identified PSMC5 (TRIP-1) as a TGF-beta type II receptor-associated, receptor-phosphorylated repressor of TGF-beta transcriptional output.

    Evidence Transient transfection, luciferase reporters, deletion mutagenesis, co-expression with Smads and constitutively active receptors

    PMID:9813058

    Open questions at the time
    • Mechanism connecting receptor phosphorylation of TRIP-1 to repression unclear
    • Endogenous relevance not shown
  6. 2000 High

    Demonstrated mechanistically that PSMC5 ATP hydrolysis drives substrate degradation, using Sp1 and an ATPase-dead dominant negative.

    Evidence In vitro reconstituted degradation, Co-IP, in vivo overexpression, ATPase-mutant/truncation dominant-negative analysis

    PMID:10816420

    Open questions at the time
    • Whether Sp1 degradation is direct via PSMC5 or requires full proteasome assembly not isolated
    • Ubiquitination requirement not detailed
  7. 2002 Medium

    Generalized the receptor-turnover/activation coupling to RAR-gamma2, integrating p38MAPK signaling with proteasome-dependent transactivation.

    Evidence Co-IP, proteasome and p38MAPK inhibitors, transcription reporter assays

    PMID:12110588

    Open questions at the time
    • Direct vs indirect coupling of turnover to activation not dissected
    • Single lab
  8. 2006 Medium

    Tied PSMC5 proteasome function to mitotic spindle checkpoint integrity and chemosensitivity to spindle poisons.

    Evidence Dominant-negative truncation, siRNA knockdown, proteasome activity, mitotic index and apoptosis assays

    PMID:16432160

    Open questions at the time
    • Mechanism linking PSMC5 to BubR1 levels unclear
    • General proteasome impairment vs specific role not separated
  9. 2009 Medium

    Extended the transcriptional role to immune gene regulation, showing PSMC5 promotes CIITA recruitment to the MHC II promoter independent of proteasome activity.

    Evidence Co-IP, ChIP, siRNA knockdown, reporter assays, proteasome inhibition

    PMID:18215421

    Open questions at the time
    • Non-proteolytic mechanism of promoter recruitment incompletely defined
    • Single lab
  10. 2008 Medium

    Defined a chromatin-level mechanism by which PSMC5 binds acetylated H3 and recruits CBP to drive promoter acetylation for transcription initiation.

    Evidence Co-IP, ChIP, siRNA knockdown, histone acetylation assays

    PMID:18662994

    Open questions at the time
    • Direct vs proteasome-mediated CBP recruitment not fully separated
    • Specificity for H3K18 mechanism unexplained
  11. 2011 Medium

    Showed PSMC5/TRIP-1 loss promotes TGF-beta-driven EMT through elevated TGF-beta receptor II, Smad3 phosphorylation, and SLUG induction.

    Evidence shRNA knockdown, western blotting, morphology/migration assays, EMT marker analysis

    PMID:21378021

    Open questions at the time
    • Whether receptor accumulation is proteasome-dependent not directly tested
    • Single cell line
  12. 2012 Medium

    Broadened immune-gene regulation to MHC class I and HLA-DM/DO, with PSMC5 controlling CBP/CIITA recruitment and H3 acetylation.

    Evidence siRNA knockdown, ChIP, transcription assays

    PMID:22771340

    Open questions at the time
    • Mechanistic distinction from MHC II regulation not addressed
    • Single lab
  13. 2014 Medium

    Distinguished a Smad-independent, AKT-mediated fibroblast-to-myofibroblast role for PSMC5/TRIP-1, separating its signaling outputs.

    Evidence siRNA, overexpression, AKT inhibitor and constitutively active AKT, alpha-SMA western, collagen contraction, Smad3 knockdown

    PMID:24528651

    Open questions at the time
    • Molecular link from PSMC5 loss to AKT activation unresolved
    • Single lab
  14. 2015 Medium

    Revealed non-degradative scaffold remodeling: PSMC5 relocates Shoc2-RAF-1 to endosomes and displaces HUWE1 to tune ubiquitylation.

    Evidence Co-IP, live-cell imaging, subcellular fractionation, ubiquitylation assay, RASopathy mutant analysis

    PMID:26519477

    Open questions at the time
    • How a proteasome ATPase displaces an E3 ligase mechanistically unclear
    • Single lab
  15. 2010 Medium

    Implicated PSMC5 in innate immune cell-death control via NLRC4/Ipaf ubiquitination and caspase-8 activation.

    Evidence Yeast two-hybrid, Co-IP, co-localization, ubiquitination and caspase-8 assays, RNAi, cell death assays

    PMID:20085538

    Open questions at the time
    • Whether PSMC5 directly mediates Ipaf ubiquitination or recruits an E3 unknown
    • Single lab
  16. 2016 Medium

    Showed an autoinflammatory NLRC4 mutant depends on enhanced SUG1 interaction for phosphorylation-independent caspase-8/FADD-dependent apoptosis.

    Evidence Comparative Co-IP of NLRC4 mutants, caspase-8 and cell death assays, FADD dependency, ubiquitination assays

    PMID:27974463

    Open questions at the time
    • Structural basis of enhanced mutant binding undefined
    • Single lab
  17. 2015 Medium

    Connected nuclear PSMC5 to behavioral plasticity through DeltaFosB complexes with gene-activating chromatin regulators in the nucleus accumbens.

    Evidence Yeast two-hybrid, endogenous Co-IP, subcellular fractionation, viral overexpression, behavioral locomotor assays

    PMID:25962134

    Open questions at the time
    • Molecular mechanism by which PSMC5 modifies DeltaFosB transcriptional output unclear
    • Single lab
  18. 2015 Medium

    Linked PSMC5 proteasome function to p53/p21 stability and radiosensitivity via an AKT/MDM2 axis in lung cancer cells.

    Evidence siRNA, AKT inhibitor, MDM2 siRNA epistasis, western blotting, clonogenic survival after irradiation

    PMID:26592665

    Open questions at the time
    • Direct PSMC5 targets upstream of AKT not identified
    • Single cell line
  19. 2020 Medium

    Showed hypoxia-induced PSMC5 drives CIITA acetylation/K63-ubiquitination, nuclear translocation, and MHC-II upregulation, affecting MSC immunoprivilege.

    Evidence Co-IP, ubiquitination/acetylation assays, siRNA, nuclear fractionation, in vivo myocardial infarction MSC transplantation model

    PMID:32770803

    Open questions at the time
    • Direct enzymatic role of PSMC5 in CIITA PTMs vs adaptor role unresolved
    • Single lab
  20. 2024 Medium

    Established disease causality: the P320R mutation and haploinsufficiency weaken 19S-20S proteasome association and impair function, activating apoptosis in patient cells.

    Evidence Patient-derived cells, proteasome activity assays, 19S-20S interface Co-IP, apoptosis marker western blotting

    PMID:38776958

    Open questions at the time
    • Structural mechanism of weakened 19S-20S docking not resolved
    • Genotype-phenotype correlation across variants not addressed
  21. 2025 Medium

    Defined the broad cellular pathology of PSMC5 loss-of-function proteasomopathy and a therapeutic entry point via integrated stress response kinase inhibition.

    Evidence Patient-derived cells, multi-omics, Drosophila knockdown, proteasome activity assays, neuronal morphology, PKR/GCN2 inhibition

    PMID:41298377

    Open questions at the time
    • Causal chain from proteasome impairment to specific neural phenotypes incomplete
    • Durability/safety of ISR kinase inhibition unaddressed
  22. 2026 Medium

    Identified a pro-tumorigenic cascade in which PSMC5 drives SMURF1-dependent K11-ubiquitination of METTL14 to remodel m6A.

    Evidence K11-linkage-specific ubiquitination assay, K263 site mutagenesis, rescue experiments, in vivo xenograft/metastasis with SMURF1 siRNA

    PMID:42212325

    Open questions at the time
    • How PSMC5 promotes SMURF1 activity toward METTL14 mechanistically unclear
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PSMC5's intrinsic biochemical activities (helicase, RNA-stimulated ATPase) and its many non-proteolytic scaffolding/transcriptional functions are mechanistically distinct from its role within the assembled 26S proteasome remains unresolved.
  • No structure of PSMC5 engaging transcription-factor activation domains
  • Whether free-pool PSMC5 acts outside the proteasome not established
  • Direct E3-ligase recruitment partners for many ubiquitination events unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1 GO:0042393 histone binding 1 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005768 endosome 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1643685 Disease 2
Partners
C-FOSCBPCIITANLRC4SHOC2SP1SRC-3VDR
Complex memberships
19S regulatory particle26S proteasome

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Yeast Sug1 (ortholog of human PSMC5) is a subunit of the 26S proteasome, not of the RNA polymerase II holoenzyme; it co-purifies with the proteasome by conventional and nickel-chelate affinity chromatography, and sug1 mutations reduce ubiquitin-dependent proteolysis. Biochemical co-purification (conventional and affinity chromatography), functional proteolysis assays in yeast mutants Nature High 8628401
1996 Mammalian Sug1 (FZA-B/mSug1, ortholog of PSMC5) is present in the nuclear 26S proteasome and interacts with c-Fos through its leucine zipper motif; depletion of FZA-B by antibody removes peptidase activity, proteasomal proteins, and c-Fos from 26S proteasome preparations. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, subcellular fractionation, antibody-depletion of proteasome activity Proceedings of the National Academy of Sciences of the United States of America High 8710853
1997 SUG1 (PSMC5) possesses intrinsic 3′→5′ DNA helicase activity that is dependent on an intact ATP-binding domain; sedimentation heterogeneity suggests it is associated with distinct protein complexes. In vitro helicase assay with recombinant protein, ATPase domain mutagenesis, sedimentation analysis The Journal of biological chemistry High 9054406
1997 Recombinant rat SUG1 (PSMC5) has Mg²⁺-dependent ATPase activity (Km ~35 µM for ATP); this activity is specifically stimulated by poly(U) and poly(C) RNA and by cellular poly(A)⁺ mRNA, but not by poly(A), poly(G), or any DNA tested, suggesting SUG1 can interact specifically with mRNA. In vitro ATPase activity assay with purified recombinant protein, UV cross-linking with [α-³²P]ATP, RNA-stimulation assays The Journal of biological chemistry High 9287326
1997 SUG1 (PSMC5) directly interacts with XPB, a subunit of the DNA repair/transcription factor TFIIH; a portion of SUG1 co-purifies with the TFIIH holocomplex under non-overexpression conditions, and overexpression of SUG1 induces transcription arrest and chromatin collapse in normal fibroblasts. Yeast two-hybrid, baculovirus co-expression, co-purification, immunopurification, nickel-chelate affinity chromatography; in vivo overexpression phenotype Nucleic acids research Medium 9173976
1998 PSMC5/mSUG1 interacts with the AF-2 domain of the vitamin D receptor (VDR) in a 1,25-(OH)₂D₃-dependent manner; overexpression of wild-type mSUG1 generates a novel ~50 kDa VDR proteolytic fragment that is blocked by proteasome inhibitors or non-hydrolyzable ATP analogue, whereas the K196H ATPase mutant that does not interact with VDR fails to produce this fragment or inhibit VDR-driven transcription. Co-immunoprecipitation, transient overexpression, proteasome inhibitor treatment, ATPase mutant (K196H), reporter gene assay, cycloheximide chase Journal of cellular biochemistry High 9831079
1998 PSMC5 (TRIP-1) associates with and is phosphorylated by the TGF-β type II receptor kinase; overexpression of TRIP-1 represses TGF-β-induced transcription from the PAI-1 promoter and inhibits Smad-driven and constitutively active TβRI-driven PAI-1 expression; two distinct non-WD40 regions are required for inhibitory activity. Transient transfection, luciferase reporter assay, deletion mutagenesis, co-expression with Smads and constitutively active receptors The Journal of biological chemistry Medium 9813058
2000 Human Sug1/PSMC5 interacts with the transcription factor Sp1 through the C-terminal ATPase-containing region of hSug1; full-length hSug1 stimulates proteasome-dependent degradation of Sp1 in vitro and in vivo, whereas an ATPase mutant of hSug1 still binds Sp1 but acts as a dominant negative, blocking Sp1 degradation; ATP hydrolysis by hSug1 is required for this process. In vitro binding, co-immunoprecipitation, in vitro reconstituted degradation assay, in vivo overexpression in NRK cells, ATPase mutant and truncation dominant-negative analysis The Biochemical journal High 10816420
2002 SUG-1 (PSMC5) is recruited to the AF-2 domain of RAR-γ2 and this interaction is required for RA-induced proteasome-mediated degradation of RAR-γ2; blocking either the p38MAPK pathway (which phosphorylates AF-1 of RAR-γ2) or 26S proteasome function impairs RA-induced transactivation by RAR-γ2, demonstrating that ligand-induced receptor turnover is coupled to transcriptional activation. Co-immunoprecipitation, proteasome inhibitor treatment, p38MAPK inhibitor treatment, transcription reporter assays The EMBO journal Medium 12110588
2008 The 19S proteasome ATPase Sug1 (PSMC5) associates with the MHC class II transactivator CIITA and with the MHC class II proximal promoter; reduction of Sug1 decreases HLA-DR promoter activity and MHC class II transcription, and dramatically reduces CIITA association with the MHC II promoter even under conditions of proteasome inhibition. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), siRNA knockdown, luciferase reporter assay, proteasome inhibition Molecular immunology Medium 18215421
2008 Sug1 (PSMC5) binds acetylated histone H3 and the histone acetyltransferase CBP; absence of Sug1 decreases histone H3 acetylation (preferentially H3K18) at the MHC II proximal promoter and reduces CBP recruitment to that promoter, indicating Sug1 regulates chromatin acetylation to initiate MHC II transcription. Co-immunoprecipitation, ChIP, siRNA knockdown, histone acetylation assays Molecular and cellular biology Medium 18662994
2009 SUG-1 (PSMC5) directly interacts with the coactivator SRC-3 and is recruited to promoters of retinoic acid target genes; SUG-1 mediates proteasomal degradation of SRC-3, and excess SUG-1 blocks RA-induced activation of RARα target genes by interfering with SRC-3 recruitment to the AF-2 domain of RARα. Co-immunoprecipitation, ChIP, overexpression/dominant-negative analysis, transcription reporter assays The Journal of biological chemistry Medium 19144644
2010 Sug1 (PSMC5) interacts with NLRC4/Ipaf (binding residues 91–253), enabling ubiquitination of Ipaf; co-expression of Sug1 with Ipaf leads to formation of cytoplasmic aggregates, caspase-8 activation, and caspase-8-dependent cell death; RNAi or dominant-negative Sug1 blocks Ipaf-induced and TNF-α/doxorubicin-induced cell death. Yeast two-hybrid, co-immunoprecipitation, co-localization, ubiquitination assay, caspase-8 activation assay, RNAi knockdown, cell death assay The Biochemical journal Medium 20085538
2015 PSMC5 (AAA+ ATPase) binds to the scaffold protein Shoc2 and triggers translocation of Shoc2 to endosomes; at endosomes, PSMC5 displaces the E3 ligase HUWE1 from the Shoc2-RAF-1 complex, attenuating ubiquitylation of Shoc2 and RAF-1; a RASopathy mutation in Shoc2 that alters its subcellular distribution disrupts accessibility to PSMC5 and consequently alters Shoc2 ubiquitylation. Co-immunoprecipitation, live-cell imaging, subcellular fractionation, ubiquitylation assay, RASopathy mutant analysis Journal of cell science Medium 26519477
2015 PSMC5 interacts with ΔFosB in the nucleus accumbens; chronic cocaine increases nuclear (but not cytoplasmic) PSMC5 levels in the NAc; overexpression of PSMC5 in the NAc promotes locomotor responses to cocaine; endogenous PSMC5 and ΔFosB form complexes with chromatin regulatory proteins associated with gene activation. Yeast two-hybrid, co-immunoprecipitation of endogenous proteins, subcellular fractionation, viral overexpression in vivo, behavioral locomotor assay PloS one Medium 25962134
2015 PSMC5 depletion in H460 lung cancer cells decreases proteasome activity, enhances AKT activation and MDM2 transcription, promotes degradation of p53 and p21, and converts radiosensitive cells to a radioresistant phenotype; inhibition of AKT or knockdown of MDM2 restores p21 levels in PSMC5-knockdown cells. siRNA knockdown, AKT inhibitor (triciribine), MDM2 siRNA, western blotting, clonogenic survival assay after irradiation Biochemical and biophysical research communications Medium 26592665
2016 The autoinflammatory NLRC4 mutant H443P shows stronger interaction with SUG1 (PSMC5) and with ubiquitinated cellular proteins than wild-type NLRC4, and constitutively activates caspase-8 and induces FADD-dependent apoptosis without requiring Ser533 phosphorylation; the phosphomimetic NLRC4 S533D mutant does not require SUG1 activity for cell death induction. Co-immunoprecipitation with NLRC4 mutants, caspase-8 activation assay, cell death assay, FADD dependency analysis, ubiquitination assay The Journal of biological chemistry Medium 27974463
2020 Sug1 (PSMC5) binds to CIITA in mesenchymal stem cells (MSCs); hypoxia upregulates Sug1, which promotes acetylation and K63-ubiquitination of CIITA, leading to CIITA nuclear translocation and MHC-II upregulation; Sug1 knockdown inactivates MHC-II expression and preserves immunoprivilege under hypoxia in vitro and in vivo. Co-immunoprecipitation, ubiquitination and acetylation assays, siRNA knockdown, nuclear fractionation, in vivo rat model of myocardial infarction with Sug1-knockdown MSC transplantation FASEB journal Medium 32770803
2024 PSMC5 P320R mutation (found in individuals with neurodevelopmental disorders) weakens the association between the 19S regulatory particle and the 20S core particle of the proteasome, impairing overall proteasome function and activating apoptosis; PSMC5 haploinsufficiency also impairs proteasome function. Patient-derived cells, proteasome activity assays, co-immunoprecipitation of 19S-20S interface, western blotting for apoptosis markers Human molecular genetics Medium 38776958
2023 PSMC5 interacts with TLR4 (via residues Glu284, Met139, Leu127, Phe283 of PSMC5); PSMC5 knockdown reduces TLR4 expression and attenuates LPS-induced NF-κB activation (IκB-α and p65 phosphorylation) in microglia; PSMC5 site mutations reduce TLR4-mediated MyD88-dependent NF-κB activation and pro-inflammatory cytokine release. siRNA/shRNA knockdown, molecular dynamics simulation, site-directed mutagenesis, co-immunoprecipitation (implied by interaction characterization), NF-κB pathway western blotting, cytokine measurement, TLR4-/- mouse model Journal of neuroinflammation Low 38001534
2025 Loss of PSMC5/RPT6 function (via 26 distinct patient variants) impairs proteasome activity leading to protein aggregation, disruption of mitochondrial homeostasis, dysregulation of lipid metabolism and immune signaling, compromised synaptic balance, neuritogenesis, and neural progenitor stemness; pharmacological inhibition of integrated stress response kinases PKR and GCN2 ameliorates immune dysregulation in patient-derived cells. Patient-derived cell models, multi-omics (transcriptomics, proteomics), Drosophila genetic knockdown, proteasome activity assays, neuronal morphology assays, pharmacological kinase inhibition Nature communications Medium 41298377
2006 A dominant-negative truncated TRIP1/S8/hSug1 (PSMC5) decreases cellular proteasome activity, increases mitotic index, and enhances apoptosis in response to spindle poisons (Taxol, vinblastine) or proteasome inhibitors; siRNA knockdown of TRIP1/hSug1 similarly reduces proteasome activity and increases cell death after spindle poison treatment, coinciding with decreased BubR1 expression. Expression cloning, stable transfection of dominant-negative truncation, siRNA knockdown, proteasome activity assay, mitotic index measurement, apoptosis assay Molecular cancer therapeutics Medium 16432160
2012 Sug1 (PSMC5) also regulates transcription of MHC class I and the atypical MHC II molecules HLA-DM and HLA-DO; reduction of Sug1 expression decreases recruitment of CBP and CIITA to MHC class I and HLA-DM/DO promoters and reduces histone H3 acetylation at these promoters. siRNA knockdown, ChIP, transcription assays Immunology letters Medium 22771340
2011 TRIP-1 (PSMC5) knockdown in A549 lung epithelial cells promotes TGF-β1-induced epithelial-mesenchymal transition; mechanistically, TRIP-1 depletion leads to increased TGF-β type II receptor levels, enhanced Smad3 phosphorylation, and induction of the transcription factor SLUG. shRNA knockdown, western blotting, morphology and migration assays, Smad3 phosphorylation measurement, EMT marker analysis American journal of physiology. Lung cellular and molecular physiology Medium 21378021
2014 TRIP-1 (PSMC5) knockdown in primary human lung fibroblasts induces α-SMA expression and myofibroblast features; this effect is mediated through AKT phosphorylation (not through Smad3), as AKT inhibition prevents α-SMA induction in TRIP-1 knockdown cells and constitutively active AKT drives collagen contraction. siRNA knockdown, plasmid overexpression, AKT inhibitor, constitutively active AKT construct, α-SMA western blotting, collagen contraction assay, apoptosis assay, Smad3 knockdown Respiratory research Medium 24528651
1998 Phosducin-like protein (PhLP) interacts with mouse SUG1 (PSMC5); inhibition of proteasome function with lactacystin leads to accumulation of high-molecular-weight ubiquitin-immunoreactive protein precipitated by PhLP antiserum, suggesting PhLP/SUG1 interaction may target PhLP for proteasomal degradation. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, proteasome inhibitor (lactacystin) treatment Biochimica et biophysica acta Low 9551090
2007 Mouse SUG1 (PSMC5) interacts with mouse Prp19 (a ubiquitin ligase involved in pre-mRNA splicing/DNA repair); the N-terminus (U-box domain) of mPrp19 binds the C-terminus of mSUG1; co-expression of mPrp19 increases cellular proteasome activity; GFP-mPrp19 co-localizes with mSUG1 in cytoplasmic speckle-like structures in the presence of proteasome inhibitor MG132. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, GFP co-localization, proteasome activity assay Biochemical and biophysical research communications Low 17349974
2006 Sug1 (PSMC5) interacts with the C-terminal tail of the unconventional myosin MYO18B; Sug1 knockdown or proteasome inhibitor treatment increases MYO18B protein levels, and MYO18B is polyubiquitinated in vivo, indicating MYO18B is a substrate targeted for proteasomal degradation via Sug1. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, siRNA knockdown, proteasome inhibitor treatment, ubiquitination assay Biochemical and biophysical research communications Low 16499872
1999 Adenovirus E1A 12S and 13S proteins bind directly to mammalian SUG1 (PSMC5), a 26S proteasome regulatory component; Ad12 E1A 13S binds SUG1 via a region distinct from conserved region 1 (which mediates increased p53 expression), and E1A co-immunoprecipitates with SUG1 in human cells infected with Ad5; SV40 large T antigen also co-immunoprecipitates with SUG1. Co-immunoprecipitation, in vitro binding assay, virus infection, 26S proteasome peptidase activity assay Oncogene Low 9927201
2026 PSMC5 promotes SMURF1-dependent K11-linked ubiquitination of METTL14 at K263, leading to METTL14 destabilization and global m⁶A remodeling; SMURF1 silencing restores METTL14 expression and attenuates PSMC5-driven tumor growth and lung metastasis in vivo. Ubiquitination assay with K11-linkage specificity, site-directed mutagenesis (K263), rescue/overexpression experiments, in vivo xenograft/metastasis model with SMURF1 siRNA International journal of biological sciences Medium 42212325

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Identification of the gal4 suppressor Sug1 as a subunit of the yeast 26S proteasome. Nature 144 8628401
2002 Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RAR gamma degradation and transactivation. The EMBO journal 126 12110588
1998 The type II transforming growth factor (TGF)-beta receptor-interacting protein TRIP-1 acts as a modulator of the TGF-beta response. The Journal of biological chemistry 101 9813058
1998 Proteasome-mediated degradation of the vitamin D receptor (VDR) and a putative role for SUG1 interaction with the AF-2 domain of VDR. Journal of cellular biochemistry 90 9831079
1997 The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor. Nucleic acids research 71 9173976
1997 SUG1, a putative transcriptional mediator and subunit of the PA700 proteasome regulatory complex, is a DNA helicase. The Journal of biological chemistry 69 9054406
2000 Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1. The Biochemical journal 58 10816420
1995 Sug1 modulates yeast transcription activation by Cdc68. Molecular and cellular biology 52 7565755
1996 Mammalian Sug1 and c-Fos in the nuclear 26S proteasome. Proceedings of the National Academy of Sciences of the United States of America 49 8710853
2008 The 19S proteasome ATPase Sug1 plays a critical role in regulating MHC class II transcription. Molecular immunology 45 18215421
1999 Expression of nuclear receptor interacting proteins TIF-1, SUG-1, receptor interacting protein 140, and corepressor SMRT in tamoxifen-resistant breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 45 10589759
2016 A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death. The Journal of biological chemistry 39 27974463
2008 Regulation of acetylation at the major histocompatibility complex class II proximal promoter by the 19S proteasomal ATPase Sug1. Molecular and cellular biology 38 18662994
2010 Interaction with Sug1 enables Ipaf ubiquitination leading to caspase 8 activation and cell death. The Biochemical journal 37 20085538
2023 PSMC5 regulates microglial polarization and activation in LPS-induced cognitive deficits and motor impairments by interacting with TLR4. Journal of neuroinflammation 35 38001534
1999 Adenovirus early region 1A protein binds to mammalian SUG1-a regulatory component of the proteasome. Oncogene 35 9927201
2015 Spatial control of Shoc2-scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5. Journal of cell science 29 26519477
1997 SUG1, a component of the 26 S proteasome, is an ATPase stimulated by specific RNAs. The Journal of biological chemistry 27 9287326
1998 Interaction of phosducin and phosducin isoforms with a 26S proteasomal subunit, SUG1. Molecular vision 24 9701609
2020 Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 32770803
2011 TRIP-1 regulates TGF-β1-induced epithelial-mesenchymal transition of human lung epithelial cell line A549. American journal of physiology. Lung cellular and molecular physiology 20 21378021
2007 Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory subunit of 26S proteasome. Biochemical and biophysical research communications 20 17349974
1998 Phosducin-like protein (PhLP), a regulator of G beta gamma function, interacts with the proteasomal protein SUG1. Biochimica et biophysica acta 19 9551090
2012 TRIP-1: a regulator of osteoblast function. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 22460930
2009 SUG-1 plays proteolytic and non-proteolytic roles in the control of retinoic acid target genes via its interaction with SRC-3. The Journal of biological chemistry 15 19144644
1997 Expression of co-factors (SMRT and Trip-1) for retinoic acid receptors in human neuroectodermal cell lines. Biochemical and biophysical research communications 15 9169003
2009 Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts. American journal of physiology. Lung cellular and molecular physiology 14 19329541
1997 Localization of genes encoding two human one-domain members of the AAA family: PSMC5 (the thyroid hormone receptor-interacting protein, TRIP1) and PSMC3 (the Tat-binding protein, TBP1). Human genetics 14 9048938
2015 Radiosensitizing effect of PSMC5, a 19S proteasome ATPase, in H460 lung cancer cells. Biochemical and biophysical research communications 13 26592665
2018 Lung epithelial-specific TRIP-1 overexpression maintains epithelial integrity during hyperoxia exposure. Physiological reports 12 29484847
2014 TRIP-1 via AKT modulation drives lung fibroblast/myofibroblast trans-differentiation. Respiratory research 12 24528651
1997 Gene structure of rat BAF60b, a component of mammalian SW1/SNF complexes, and its physical linkage to the growth hormone gene and transcription factor SUG/proteasome p45 gene. Gene 12 9427560
2021 PSMC5 Promotes Proliferation and Metastasis of Colorectal Cancer by Activating Epithelial-Mesenchymal Transition Signaling and Modulating Immune Infiltrating Cells. Frontiers in cell and developmental biology 11 34336824
2006 MYO18B interacts with the proteasomal subunit Sug1 and is degraded by the ubiquitin-proteasome pathway. Biochemical and biophysical research communications 11 16499872
2015 PSMC5, a 19S Proteasomal ATPase, Regulates Cocaine Action in the Nucleus Accumbens. PloS one 10 25962134
2006 Inhibition of TRIP1/S8/hSug1, a component of the human 19S proteasome, enhances mitotic apoptosis induced by spindle poisons. Molecular cancer therapeutics 10 16432160
1997 Identification of a phylogenetically conserved Sug1 CAD family member that is differentially expressed in the mouse nervous system. Journal of neurobiology 10 9407011
2018 TRIP-1 Promotes the Assembly of an ECM That Contains Extracellular Vesicles and Factors That Modulate Angiogenesis. Frontiers in physiology 9 30158875
2025 A molecular framework for the GS2-SUG1 module-mediated control of grain size and weight in rice. Nature communications 8 40287410
1996 The porcine gene TBP10 encodes a protein homologous to the human tat-binding protein/26S protease subunit family. Mammalian genome : official journal of the International Mammalian Genome Society 8 8833236
2024 PSMC5 insufficiency and P320R mutation impair proteasome function. Human molecular genetics 6 38776958
2012 Role of Sug1, a 19S proteasome ATPase, in the transcription of MHC I and the atypical MHC II molecules, HLA-DM and HLA-DO. Immunology letters 6 22771340
2008 Recognition and characterization of TGF-beta receptor interacting protein 1 (TRIP-1) containing WD40 repeats from Clonorchis sinensis by bioinformatics, cloning, and expression in Escherichia coli. Parasitology research 6 18626661
1997 Gene coding for the transcription factor, SUG/proteasome, p45 is located nearly 40 kb downstream from the rat growth hormone gene. Gene 6 9370298
2024 Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies. medRxiv : the preprint server for health sciences 5 38293138
1998 The DUG gene of Drosophila melanogaster encodes a structural and functional homolog of the S. cerevisiae SUG1 predicted ATPase associated with the 26S proteasome. Gene 5 9469929
1998 Cloning and characterization of Pros45, the Drosophila SUG1 proteasome subunit homolog. Molecular & general genetics : MGG 5 9738875
2023 Insights into the Structure and Function of TRIP-1, a Newly Identified Member in Calcified Tissues. Biomolecules 4 36979349
2018 TRIP-1 in the extracellular matrix promotes nucleation of calcium phosphate polymorphs. Connective tissue research 4 29745814
1998 Genomic structure and chromosomal location of the human TGFbeta-receptor interacting protein-1 (TRIP-1) gene to 1p34.1. FEBS letters 4 9599024
2025 Strengthening the Role of PSMC5 as a Potential Gene Associated with Neurodevelopmental Disorders. International journal of molecular sciences 3 40650163
2025 Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies. Nature communications 2 41298377
2026 PSMC5 Orchestrates an Immunosuppressive Niche and Metastasis in Colorectal Cancer via SMURF1-Mediated K11-Linked Ubiquitination of METTL14. International journal of biological sciences 0 42212325
2024 Diversity, Distribution, and Chromosomal Rearrangements of TRIP1 Repeat Sequences in Escherichia coli. Genes 0 38397225
2013 WITHDRAWN: TRIP-1 interacts with ezrin to regulate ezrin phosphorylation, cell protrusion formation and cell migration. Cellular signalling 0 24012495

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