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Showing PSMD14 — RPN11 is a alias.

PSMD14

Ubiquitin C-terminal hydrolase PSMD14 · UniProt O00487

Length
310 aa
Mass
34.6 kDa
Annotated
2026-06-10
90 papers in source corpus 51 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMD14 (POH1/Rpn11) is the essential zinc-dependent JAMM-family metalloprotease deubiquitinase of the 19S proteasome lid that couples substrate deubiquitination to ATP-dependent proteolysis, removing poly-ubiquitin chains en bloc as substrates are translocated into the degradation machinery (PMID:12183636, PMID:14581483). Its catalytic activity resides in the MPN+/JAMM motif, whose conserved active-site residues are required for viability in yeast and human cells and for proteasomal degradation; active-site mutation abolishes deubiquitination and is lethal (PMID:12183636, PMID:12370088, PMID:17237285). Structural and biochemical work established that Rpn11 is a promiscuous, low-affinity deubiquitinase lacking ubiquitin-linkage specificity at the level of the isolated MPN domain, and that full activation requires incorporation into the 26S proteasome and ATP hydrolysis—premature activity being prevented by an Insert-1 barrier loop and an unstable catalytic loop (PMID:24463465, PMID:24516147). Substrate-driven ubiquitin binding switches the Ins-1 loop to an active conformation in a step that is rate-limiting and accelerated by mechanical translocation, placing Rpn11 in direct kinetic competition with ATPase-driven ubiquitin unfolding (PMID:28844860); ubiquitin binding also acts allosterically through Rpn10 to stabilize the engagement-competent proteasome state and speed turnover (PMID:40411784). Within and beyond the proteasome, PSMD14 preferentially processes K63-linked chains (PMID:19214193, PMID:25389291), a specificity it exploits at sites of DNA double-strand breaks, where it removes RNF8/RNF168-generated K63 chains to limit 53BP1 accumulation, counter the RAP80 barrier to end resection, and promote homologous recombination (PMID:22909820, PMID:24013561). Loss of PSMD14 causes polyubiquitin accumulation, G0/G1 arrest and senescence, distinguishing 19S from 20S function (PMID:17237285, PMID:19732767). Independently of bulk degradation, PSMD14 deubiquitinates and stabilizes numerous substrates—E2F1, SNAIL, TGF-β receptors and Smad3, ALK2, ERα, β-catenin, MYC, GRB2 and others—removing K48- or K63-linked chains to control their stability and downstream signaling, frequently in cancer contexts and often within transcriptional positive-feedback loops (PMID:26510456, PMID:29331416, PMID:30745168, PMID:31685442, PMID:38017133, PMID:37844756, PMID:38061486). PSMD14 further acts on chromatin as a non-proteasomal H2AK119 deubiquitinase in complex with NSD2 to license H3K36 methylation and transcription (PMID:37935198), regulates K63-dependent Golgi-to-ER retrograde transport and macroautophagy (PMID:32210007), and is targeted by zinc-chelating inhibitors including capzimin and thiolutin that stabilize proteasome substrates and induce the unfolded protein response (PMID:28244987, PMID:28459440).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 High

    Establishing whether the proteasome lid contains an intrinsic deubiquitinase resolved how ubiquitin is removed during degradation: Rpn11 was identified as a JAMM metalloprotease whose activity is mechanistically coupled to substrate proteolysis.

    Evidence Active-site mutagenesis (rpn11AXA) with yeast lethality and in vitro reconstituted degradation of ubiquitinated Sic1; MPN+ motif mutagenesis with proteolysis defects

    PMID:12183636 PMID:12370088

    Open questions at the time
    • Did not resolve the structural basis of substrate engagement
    • Linkage specificity not yet defined
  2. 2003 High

    Defining how proteasomal deubiquitination is partitioned showed Rpn11 and Ubp6 play complementary, non-redundant roles and confirmed Rpn11 as a metal-dependent enzyme requiring an intact lid for coupling to degradation.

    Evidence Proteasome purification from yeast mutants, in vitro DUB assays, metal chelator sensitivity, synthetic lethality genetics

    PMID:14581483

    Open questions at the time
    • Mechanism coupling deubiquitination to translocation not defined
    • Metal identity inferred, not structurally resolved
  3. 2004 High

    Dissecting Rpn11 into separable domains revealed a catalytic-independent C-terminal function in mitochondrial morphology, indicating roles beyond proteasomal DUB activity.

    Evidence Yeast RPN8-RPN11 chimera analysis, intragenic complementation, mitochondrial microscopy, cell cycle analysis

    PMID:15018611

    Open questions at the time
    • Molecular mechanism of the mitochondrial function unresolved
    • Not extended to mammalian cells in this work
  4. 2007 High

    Testing requirement in human cells confirmed the JAMM motif is essential for viability and 26S function, validating PSMD14 catalysis as the operative human activity.

    Evidence siRNA knockdown with wild-type vs JAMM-mutant rescue, viability and polyubiquitin accumulation assays in HeLa cells

    PMID:17237285

    Open questions at the time
    • Did not address non-proteasomal functions
    • Substrate scope not examined
  5. 2009 High

    Defining linkage specificity and downstream phenotype showed proteasome-associated PSMD14 is a K63-specific metalloDUB and that 19S loss produces cell cycle arrest distinct from 20S inhibition.

    Evidence Seven-step chromatographic co-fractionation with linkage-specific assays and inhibitor profiling; siRNA with flow cytometry and comparison to PSMB5

    PMID:19214193 PMID:19732767

    Open questions at the time
    • K63 specificity at the isolated enzyme level not yet reconciled with later structural promiscuity
    • Direct substrates driving arrest not identified
  6. 2009 Medium

    Early substrate studies hinted that PSMD14 deubiquitinates specific proteins (c-Jun, ErbB2) in a manner not strictly coupled to degradation, foreshadowing degradation-independent stabilization roles.

    Evidence Ectopic overexpression and active-site mutagenesis for c-Jun; siRNA DUB screen and Western/flow cytometry for ErbB2

    PMID:16569633 PMID:19436748

    Open questions at the time
    • Single-lab Co-IP/ubiquitination without reciprocal validation
    • Selectivity claims rest on limited substrate panels
  7. 2013 High

    Positioning PSMD14 in DNA repair established that it processes K63 chains at break sites to limit 53BP1, counter the RAP80 resection barrier, and bias repair toward homologous recombination.

    Evidence siRNA knockdown and co-depletion, immunofluorescence of DSB foci, K63-Ub chromatin analysis, survival assays

    PMID:22909820 PMID:24013561

    Open questions at the time
    • Whether this is proteasome-dependent or free-DUB activity not fully resolved
    • Direct chromatin substrates not enumerated
  8. 2014 High

    Crystallographic and biochemical analyses resolved the structural logic of Rpn11: it is an intrinsically promiscuous, low-affinity DUB whose activation is gated by proteasome incorporation and ATP hydrolysis.

    Evidence Rpn11-Rpn8 heterodimer crystal structures, nanobody-assisted crystallization, cryo-EM docking, mutagenesis, defined-chain in vitro DUB kinetics

    PMID:24463465 PMID:24516147 PMID:25389291

    Open questions at the time
    • The ubiquitin-bound active conformation not yet captured at this stage
    • Reconciliation with cellular K63 preference incomplete
  9. 2015 High

    An in vivo substrate paradigm showed PSMD14 stabilizes E2F1 to drive oncogenic transcription, exemplifying degradation-independent substrate control in mammals.

    Evidence Reciprocal Co-IP, in vivo ubiquitination, conditional Poh1 knockout mouse liver, xenografts

    PMID:26510456

    Open questions at the time
    • Whether stabilization is proteasome-associated or free-enzyme not dissected
    • Linkage type on E2F1 not specified
  10. 2017 High

    Capturing the ubiquitin-bound state and developing selective inhibitors defined the mechanochemical activation switch and validated PSMD14 as a druggable target competing with ATPase-driven ubiquitin unfolding.

    Evidence Ubiquitin-bound Rpn11 crystal structure with single-molecule and ensemble DUB assays; capzimin and thiolutin zinc-chelation inhibition with proteomics and cell viability

    PMID:28244987 PMID:28459440 PMID:28844860

    Open questions at the time
    • Inhibitor selectivity over related JAMM proteases is limited
    • In vivo therapeutic window not established in these studies
  11. 2019 High

    Expanding the substrate repertoire established broad degradation-independent stabilization activity across SNAIL, TGF-β receptors, ALK2 and GRB2, frequently via removal of specific K48 or K63 chains in cancer.

    Evidence Mass spectrometry interactomics, Co-IP, linkage-specific ubiquitination assays, conditional knockout mice, xenograft and metastasis models

    PMID:29331416 PMID:30315153 PMID:30745168 PMID:31634528 PMID:31685442

    Open questions at the time
    • Most substrate studies are single-lab without reciprocal cross-validation
    • Whether substrate DUB activity requires proteasome incorporation often untested
  12. 2020 High

    A trafficking and autophagy role showed PSMD14 acts on cellular K63 chains to enable Golgi-to-ER retrograde transport, distinct from 20S proteasome function.

    Evidence High-content siRNA ubiquitinome screen, capzimin treatment, trafficking-marker microscopy, autophagy flux, 19S vs 20S comparison

    PMID:32210007

    Open questions at the time
    • Direct K63-ubiquitinated trafficking substrates not identified
    • Mechanism of recruitment to Golgi unresolved
  13. 2023 High

    Demonstrating a chromatin-resident, proteasome-independent activity revealed PSMD14 as an H2AK119 deubiquitinase in an NSD2 complex that licenses transcription, establishing a non-proteasomal epigenetic role.

    Evidence ChIP-seq, chromatin Co-IP, histone H2AK119 deubiquitination assays, integrative epigenomics, inhibitor studies

    PMID:37935198

    Open questions at the time
    • How PSMD14 is partitioned between proteasome and chromatin pools unclear
    • Generality across cell types beyond myeloma not established
  14. 2025 High

    Mechanistic refinement defined PSMD14 as an allosteric ubiquitin sensor that accelerates proteasomal turnover via Rpn10, while a wave of substrate studies (MYC, ERα, METTL3, LDHA, β-catenin, PD-L1, BCKDK, IMPDH2, metabolic and immune regulators) extended its degradation-independent stabilization activity into metabolism, immunity, and feedback transcriptional loops.

    Evidence smFRET, interface mutagenesis and reconstituted degradation for the allosteric mechanism; Co-IP, linkage-specific ubiquitination, conditional knockouts and PDX/syngeneic models for substrates

    PMID:37844756 PMID:38017133 PMID:38696072 PMID:39146936 PMID:40411784 PMID:41051446 PMID:41608571 PMID:41876842 PMID:41981629

    Open questions at the time
    • Substrate studies are predominantly single-lab and context-specific
    • Whether individual substrate DUB events occur at the proteasome or by a free enzyme pool largely untested
  15. 2025 Medium

    Structural studies began to reveal non-canonical, ubiquitin-independent uses of Rpn11—as a midnolin Ubl receptor and an ODC translocation gateway—and a TXNL1-mediated regulatory contact in processing-state proteasomes.

    Evidence Time-resolved and multi-state cryo-EM of TXNL1-, MIDN-, and ODC-bound proteasomes (preprints)

    PMID:bio_10.1101_2024.11.08.622731 PMID:bio_10.1101_2025.02.22.639686 PMID:bio_10.1101_2025.11.15.688597

    Open questions at the time
    • Preprints not yet peer-reviewed
    • Functional consequences in cells not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PSMD14 is physically and functionally partitioned between its proteasome-bound deubiquitinase role and its numerous proteasome-independent activities on individual substrates and chromatin, and what governs substrate selection at the cellular level.
  • No systematic distinction between proteasome-associated and free-enzyme substrate processing
  • Recruitment determinants for specific substrates unknown
  • Quantitative cellular pools of proteasomal vs non-proteasomal PSMD14 not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 1 GO:0140299 molecular sensor activity 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1 R-HSA-4839726 Chromatin organization 1 R-HSA-5653656 Vesicle-mediated transport 1
Partners
E2F1MYCNSD2PSMD10PSMD7SNAILTGFBR1TXNL1
Complex memberships
19S proteasome regulatory particle (lid)26S proteasomePSMD14-NSD2 chromatin complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Rpn11 is a metalloprotease deubiquitinase (DUB) residing in the proteasome lid subcomplex. Its JAMM motif (EX(n)HXHX(10)D) constitutes the active site; mutation of the predicted catalytic histidines to alanine (rpn11AXA) was lethal in yeast and caused mutant proteasomes—which assembled normally—to fail to deubiquitinate or degrade ubiquitinated Sic1 in vitro, demonstrating that Rpn11-mediated deubiquitination is coupled to substrate degradation. Active-site mutagenesis (rpn11AXA), yeast genetics (lethality), in vitro reconstituted degradation assay with purified mutant proteasomes Science High 12183636
2002 The MPN+ motif (five conserved polar residues resembling metalloprotease active-site residues) is essential for Rpn11 function. Single amino acid substitutions in MPN+ residues cause slow growth, temperature sensitivity, and proteasome-dependent proteolysis defects in yeast, while a conserved Cys outside MPN+ is not essential. Site-directed mutagenesis of MPN+ motif residues, yeast phenotypic analysis, proteasome proteolysis assays BMC Biochemistry High 12370088
2003 Rpn11 and Ubp6 serve complementary roles in proteasomal deubiquitination. Proteasomes purified from rpn11 catalytic-motif mutants or ubp6 null strains both show slower deubiquitination rates; the double mutant is synthetically lethal. Rpn11-containing proteasomes show sensitivity to metal chelators consistent with Rpn11 being a metalloprotein. Degradation requires the intact lid (lidless proteasomes deubiquitinate but do not degrade ubiquitinated protein). Purification of proteasomes from yeast mutants, in vitro deubiquitination assays, metal chelator treatment, synthetic lethality genetics Journal of Biological Chemistry High 14581483
2004 Rpn11 has two separable functional domains: its N-terminal MPN+/JAMM catalytic domain mediates proteasome-associated deubiquitination required for proteolysis, while a distinct C-terminal domain is required for mitochondrial morphology maintenance and is independent of catalytic activity. Overexpression of wild-type Rpn8 rescues cell cycle but not mitochondrial defects of rpn11 C-terminal mutant (mpr1-1). RPN8-RPN11 chimera analysis confirmed the C-terminal region of Rpn11 is necessary and sufficient to rescue mitochondrial phenotypes. Yeast genetics, RPN8-RPN11 chimera expression, intragenic complementation, mitochondrial morphology microscopy, cell cycle analysis Biochemical Journal High 15018611
2006 POH1/PSMD14 deubiquitinates c-Jun in mammalian cells. Ectopic POH1 expression in HEK293 cells decreased c-Jun ubiquitination, stabilized c-Jun protein, redistributed it to the nucleus, and increased AP1-mediated gene expression. Mutation of Cys-120 in the MPN+ motif reduced these effects. The stabilization appeared selective for c-Jun among tested proteasomal substrates. Ectopic overexpression, ubiquitination assays, reporter assays for AP1 transcription, active-site mutagenesis (C120 mutation) Journal of Biological Chemistry Medium 16569633
2007 The JAMM zinc metalloproteinase motif of human POH1/PSMD14 is essential for cell viability and 26S proteasome function. RNAi knockdown of endogenous POH1 reduced viability and elevated polyubiquitinated proteins; rescue with wild-type POH1 restored viability, but a JAMM active-site double histidine-to-alanine mutant failed to rescue, confirming catalytic activity is required. siRNA knockdown, RNAi complementation with wild-type vs. JAMM-mutant POH1, cell viability assays, polyubiquitin accumulation analysis in HeLa cells Molecular Cancer Therapeutics High 17237285
2009 POH1/PSMD14 within the PA700/19S proteasome is a K63-specific deubiquitinase. Biochemical fractionation of HeLa cell extracts through seven chromatographic steps co-purified the K63-specific DUB activity with the 19S proteasome. This activity was intrinsic to PA700 and was insensitive to N-ethylmaleimide and ubiquitin aldehyde (ruling out cysteine-based DUBs), consistent with JAMM metalloprotease activity. None of the complexes cleaved K6, K11, K29, K48, or alpha-linked chains. Multi-step chromatographic co-fractionation, linkage-specific deubiquitination assays, inhibitor profiling (NEM, ubiquitin aldehyde), gel filtration EMBO Journal High 19214193
2009 POH1/PSMD14 knockdown causes apparent loss of ErbB2 protein in HeLa cells, explained at least partially by accumulation of higher-molecular-weight ubiquitinated forms of ErbB2 rather than increased degradation rate. POH1 appears to deubiquitinate ErbB2 in a manner not necessarily coupled to proteasomal degradation. Cell-surface ErbB2 levels were only mildly affected. siRNA library screen for DUBs, Western blot, flow cytometry for surface ErbB2, comparison with proteasome inhibitor epoxomicin PLoS ONE Medium 19436748
2009 PSMD14 knockdown in carcinoma cell lines causes G0/G1 cell cycle arrest and cellular senescence, associated with downregulation of cyclin B1-CDK1-CDC25C and cyclin D1, upregulation of p21 and p27, and markedly reduced retinoblastoma protein phosphorylation. These effects are distinct from those caused by knockdown of PSMB5 (20S subunit), indicating that the 19S and 20S proteasome subunits have distinct biological functions. siRNA knockdown, flow cytometry (cell cycle), Western blot for cell cycle regulators, comparative siRNA of PSMB5 Experimental Cell Research Medium 19732767
2012 POH1/PSMD14 processes K63-linked polyubiquitin chains generated at DNA double-strand break (DSB) sites, thereby limiting 53BP1 accumulation (via antagonism of RNF8/RNF168-mediated K63-Ub) and promoting JMJD2A chromatin retention. POH1 also promotes RAD51 loading in homologous recombination independently of 53BP1. POH1-deficient cells show increased sensitivity to DNA damaging agents. siRNA knockdown, immunofluorescence for DSB foci (53BP1, RAD51, γH2AX), K63-Ub chromatin analysis, cell survival assays EMBO Journal High 22909820
2013 POH1 relieves the barrier posed by RAP80 to DNA end resection in G2 phase. POH1 depletion enlarges 53BP1 and ubiquitin chain foci and prevents formation of an RPA-positive resection core. Co-depletion of POH1 with RAP80, BRCC36, or ABRAXAS restores the resection-competent core, suggesting POH1 removes ubiquitin chains in the IRIF core that RAP80 reads, enabling transition from NHEJ to HR. BRCA1 and POH1 act as distinct but interfacing barriers to ubiquitin chain removal. siRNA co-depletion experiments, immunofluorescence for DSB factors (53BP1, RAP80, RPA, ubiquitin FK2), cell cycle-staged analysis Nucleic Acids Research High 24013561
2014 Crystal structures of the Rpn11-Rpn8 heterodimer at 2.0 Å resolution reveal that Rpn11 lacks a conserved surface for ubiquitin Ile44-patch binding, does not contact the proximal side of the scissile isopeptide bond, and exhibits no ubiquitin linkage specificity. Two distinct interfaces mediate the Rpn11-Rpn8 interaction. Mutational studies confirm these structural features explain how Rpn11 functions as a promiscuous, cotranslocational deubiquitinase. X-ray crystallography (Zn2+-free and Zn2+-bound structures), site-directed mutagenesis, biochemical DUB assays Nature Structural & Molecular Biology High 24463465
2014 Crystal structures of the Rpn8-Rpn11 MPN-domain heterodimer (obtained via nanobody-assisted crystallization) reveal that full Rpn11 activation requires incorporation into the 26S proteasome and is dependent on ATP hydrolysis. Premature activation is prevented by: (1) low intrinsic ubiquitin affinity, (2) an insertion segment acting as a physical barrier across the substrate access channel, and (3) a conformationally unstable catalytic loop. Docking into proteasome EM density shows Rpn11 contacts ATPase subunits that stabilize the active conformation. X-ray crystallography (three structures), cryo-EM density docking, nanobody-assisted crystallization, DUB activity assay with model substrate PNAS High 24516147
2014 Rpn11 and Ubp6 process K11- and K63-linked ubiquitin chains with comparable efficiencies (increasing with chain length), whereas proteasomal processing of K48-linked chains is inversely correlated with chain length. Incorporation into proteasomes enhances Rpn11 enzymatic efficiency by roughly 2 orders of magnitude, partly by relieving autoinhibition by its C-terminus. Rpn11 shows a random cleavage mode on K48 chains (broad/endo), while Ubp6 shows endo-chain preference on K48. In vitro DUB assays with defined ubiquitin conjugates (homogeneous K11, K48, K63 chains of varying lengths, heterogeneous chains), fluorescently labeled Ub chains, purified proteasomes vs isolated DUBs Journal of Biological Chemistry High 25389291
2015 POH1/PSMD14 deubiquitylates and stabilizes E2F1. POH1 physically binds E2F1 and removes ubiquitin from it, preventing its proteasomal degradation. Conditional knockout of Poh1 in primary mouse liver cells reduces E2F1 protein levels. Stabilized E2F1 upregulates Survivin and FOXM1, promoting liver cancer cell tumor growth. Co-immunoprecipitation, in vivo ubiquitination assays, conditional Poh1 knockout mouse model, Western blot, xenograft mouse model Nature Communications High 26510456
2017 Rpn11 DUB activity is coupled to substrate translocation by the AAA+ ATPase motor via a conformational switch of the Insert-1 (Ins-1) loop. Ubiquitin binding induces Ins-1 transition from an inactive closed state to an active β-hairpin; this switch is rate-limiting for deubiquitination and is strongly accelerated by mechanical substrate translocation. Deubiquitination by Rpn11 and ubiquitin unfolding by the ATPases are in direct competition, requiring rapid Rpn11 activation to prevent ubiquitin co-degradation. X-ray crystallography (ubiquitin-bound Rpn11 structure), mutagenesis, in vitro single-molecule and ensemble DUB assays, biochemical translocation-deubiquitination coupling assays Molecular Cell High 28844860
2017 Quinoline-8-thiol derivative capzimin is a selective inhibitor of proteasomal Rpn11/PSMD14 that inhibits the JAMM metalloprotease by chelating its active-site zinc. Capzimin (>5-fold selectivity for Rpn11 over related JAMM proteases) stabilizes polyubiquitinated proteasome substrates, induces unfolded protein response, and blocks cancer cell proliferation including bortezomib-resistant cells. Biochemical DUB activity assays, proteomic analysis of stabilized substrates, cell viability assays, selectivity profiling against related JAMM proteases and metalloenzymes Nature Chemical Biology High 28244987
2017 Thiolutin, a disulfide-containing antibiotic, is a zinc chelator that inhibits the JAMM metalloprotease Rpn11/PSMD14 of the 19S proteasome in its reduced form. It also inhibits related JAMM metalloproteases Csn5, AMSH, and BRCC36. Biochemical DUB inhibition assays, zinc chelation characterization, zinc-binding experiments with Rpn11 and related JAMM enzymes Nature Chemical Biology High 28459440
2018 PSMD14 deubiquitylates SNAIL (EMT transcription factor), preventing its ubiquitin-mediated proteasomal degradation, thereby stabilizing SNAIL protein. Mass spectrometry identified PSMD14 as a SNAIL-interacting DUB. PSMD14 knockdown blocks SNAIL-induced EMT, suppresses tumor cell migration and invasion in vitro, and inhibits metastasis in vivo. Mass spectrometry interactome screen, co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown with migration/invasion assays, xenograft metastasis model Cancer Letters High 29331416
2018 Epidithiodiketopiperazines (ETPs) inhibit proteasomal degradation by targeting Rpn11/POH1/PSMD14, the essential proteasomal DUB. ETPs also inhibit related JAMM proteases Csn5 and AMSH. An improved ETP (SOP11) stabilizes a subset of polyubiquitinated proteasome substrates, induces the unfolded protein response, and causes cell death. In vitro reconstituted proteasome-mediated protein degradation assay, biochemical Rpn11 inhibition assays, cellular proteasome substrate stabilization, UPR reporter assays Cell Chemical Biology High 30146242
2018 POH1/PSMD14 deubiquitinates pro-IL-1β by removing K63-linked polyubiquitin chains, decreasing its susceptibility to cleavage and mature IL-1β production. POH1 physically interacts with pro-IL-1β. Myeloid cell-specific POH1 deletion aggravates LPS-induced systemic inflammation and alum-induced peritonitis in vivo. Co-immunoprecipitation, K63-specific deubiquitination assay, myeloid-specific conditional knockout mice, in vivo inflammation models (LPS, alum peritonitis), IL-1β production measurement Nature Communications High 30315153
2019 PSMD14 deubiquitinates and stabilizes GRB2 via inhibiting its ubiquitin-mediated proteasomal degradation, promoting HCC proliferation, migration, and invasion. Co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown, overexpression experiments, xenograft and metastasis mouse models Cancer Letters Medium 31634528
2019 PSMD14 deubiquitinates the ALK2 (BMP type I receptor) by removing K48-linked ubiquitin chains added by Smurf1 E3 ligase, thereby stabilizing ALK2 and promoting BMP6 signaling pathway activation. This function is stated to be independent of its intrinsic role in the 26S proteasome. PSMD14 was identified via siRNA DUB library screen. siRNA DUB library screen, immunoblot, co-immunoprecipitation, K48-specific ubiquitination assays, xenograft colorectal cancer model EBioMedicine Medium 31685442
2019 POH1 deubiquitinates TGF-β receptors (TGFBR1 and TGFBR2) and caveolin-1 (CAV1), preventing lysosome pathway-mediated turnover of TGF-β receptors and thereby hyperactivating TGF-β signaling. POH1-deficient mouse hepatocytes show severely downregulated TGF-β receptor levels. This promotes HCC metastatic properties in vitro and in vivo. Western blotting, co-immunoprecipitation, ubiquitination assays, conditional Poh1 knockout mouse (Mx-Cre+, poh1f/f), xenograft and metastasis models EBioMedicine High 30745168
2020 PSMD14 depletion or pharmacological inhibition (capzimin) causes retention of Atg9A and Rab1A at the Golgi apparatus, blocking Golgi-to-ER retrograde transport and consequently inhibiting macroautophagy. PSMD14 acts specifically on K63-linked ubiquitin chains in cells. Inhibition of the 20S proteasome did not recapitulate these trafficking effects, indicating a specific role for PSMD14/K63-Ub in Golgi-to-ER retrograde transport. High-content siRNA screening (1187 ubiquitinome genes), APP trafficking reporter, siRNA knockdown, capzimin treatment, fluorescence microscopy for Golgi/ER trafficking markers, autophagy flux assays Cells High 32210007
2021 Arsenite inhibits PSMD14/Rpn11 metalloprotease DUB activity by substituting zinc in the MPN/JAMM domain. The proteasomal adaptor AIRAP can directly relieve this PSMD14/Rpn11 inhibition, suggesting a metal relay mechanism between arsenylated PSMD14 and AIRAP to restore proteasomal DUB function during arsenite stress. Direct arsenite binding assay, in vitro Rpn11 DUB inhibition assay, AIRAP interaction and relief-of-inhibition experiments Biomolecules Medium 34572530
2021 PSMD14 decreases K63-linked ubiquitination on PKM2, shifts the PKM2 oligomeric equilibrium from tetramers toward dimers/monomers, diminishes pyruvate kinase enzymatic activity, and induces nuclear translocation of PKM2, thereby promoting aerobic glycolysis in ovarian cancer cells. Co-immunoprecipitation, K63-specific ubiquitination assays, PKM2 oligomeric state analysis (native PAGE), pyruvate kinase activity assay, nuclear fractionation, siRNA knockdown/overexpression Molecular Oncology Medium 34382324
2022 PSMD14 deubiquitinates and stabilizes LRPPRC by inhibiting its ubiquitination, thereby suppressing autophagy through the LRPPRC/Beclin1-Bcl-2/SQSTM1 signaling pathway in ovarian cancer cells. Co-immunoprecipitation, ubiquitination assays, autophagy flux assays, siRNA knockdown, xenograft and metastasis mouse models BBA Molecular Basis of Disease Medium 36328147
2023 PSMD14 acts as a histone H2AK119 deubiquitinase independently of the 19S regulatory particle, functioning on chromatin in complex with NSD2. This non-proteasomal PSMD14 activity facilitates NSD2-directed H3K36 dimethylation and transcriptional activation of target genes including RELA, driving myelomagenesis. RELA in turn transactivates PSMD14, forming a positive feedback loop. ChIP-seq, co-immunoprecipitation (chromatin-bound PSMD14-NSD2 complex), histone H2AK119 deubiquitination assays, integrative genomic/epigenomic analyses, PSMD14 inhibitor studies Molecular Cell High 37935198
2023 POH1 deubiquitinates and stabilizes the MYC protein, which potentiates acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). Pancreatic-specific deletion of Poh1 attenuates ADM and impairs pancreatic carcinogenesis in murine models. Pancreatic-specific conditional Poh1 knockout mouse, co-immunoprecipitation, in vivo ubiquitination assay, ADM murine models Cancer Letters High 37844756
2023 POH1 directly interacts with Smad3, removes poly-ubiquitin modifications from Smad3, stabilizes it, and thereby facilitates TGF-β1-mediated lung cancer cell invasion and metastasis. Co-immunoprecipitation, colocalization analysis, in vitro deubiquitination, half-life assay, functional migration/invasion assays, xenograft liver metastasis model Cancer Letters Medium 38061486
2023 PSMD14 stabilizes ERα by removing K48-linked polyubiquitin chains, thereby maintaining ERα protein levels and ERα transcriptome in breast cancer. ERα reciprocally binds the PSMD14 promoter to promote its transcription, forming a positive feedback loop. In endocrine-resistant models, PSMD14 inhibition destabilizes the resistant ERα Y537S mutant and restores tamoxifen sensitivity. siRNA DUB library screen, co-immunoprecipitation, K48-specific ubiquitination assay, ChIP assay, endocrine-resistance model, in vivo xenograft Oncogene High 38017133
2024 PSMD14 deubiquitinates β-catenin by decreasing its K48-linked ubiquitination, preventing β-catenin proteasomal degradation and stabilizing it, thereby promoting GBM cell proliferation and invasion. PSMD14 directly interacts with β-catenin. Co-immunoprecipitation, K48-specific ubiquitination assay, siRNA knockdown, rescue with β-catenin overexpression, xenograft mouse model BioFactors Medium 38696072
2024 RPN11/PSMD14 deubiquitinates and stabilizes METTL3, an m6A RNA methyltransferase. Stabilized METTL3 enhances m6A modification and expression of ACSS3, which generates propionyl-CoA to upregulate lipid metabolism genes via histone propionylation. Hepatocyte-specific RPN11 knockout mice are protected from diet-induced liver steatosis, insulin resistance, and steatohepatitis. Hepatocyte-specific conditional RPN11 knockout mice, co-immunoprecipitation, ubiquitination assays, m6A sequencing, metabolomics, in vivo diet-induced NAFLD models, pharmacological inhibition (capzimin) Cell Metabolism High 39146936
2025 Rpn11 functions as an allosteric ubiquitin sensor at the 26S proteasome. After substrate recruitment, ubiquitin binding to Rpn11 interferes with conformation-specific interactions of the ubiquitin receptor Rpn10, thereby stabilizing the engagement-competent proteasome state and expediting substrate insertion into the ATPase motor. This allosteric mechanism allows poly-ubiquitin chains or multiple mono-ubiquitins to promote up to 4-fold faster proteasomal turnover. Biochemical assays, active-site and interface mutagenesis, single-molecule FRET (smFRET) measurements of proteasome conformational states, reconstituted degradation assays Cell Reports High 40411784
2025 PSMD14 prevents SLC7A11 ubiquitination and proteasomal degradation by binding to it; glucocorticoids impede this PSMD14-SLC7A11 interaction, causing SLC7A11 degradation, cystine insufficiency, and osteocyte ferroptosis in GIOP. Bone-targeting AAV-mediated PSMD14 overexpression stabilizes SLC7A11 and attenuates both osteocyte ferroptosis and bone loss. Co-immunoprecipitation, ubiquitination assays, AAV-mediated overexpression in mouse model, GPX4 conditional KO, pharmacological ferroptosis inhibitors, high-throughput virtual screening Advanced Science Medium 40444470
2025 PSMD14 directly binds and deubiquitinates LDHA to stabilize it, increasing intracellular lactate, which elevates histone lactylation (H3K18la) to transcriptionally activate ACLY and promote lipid biosynthesis and pancreatic cancer progression. Co-immunoprecipitation, ubiquitination assays, histone lactylation measurements, ACLY expression analysis, patient-derived xenograft (PDX) models Advanced Science Medium 41051446
2025 PSMD14 directly deubiquitinates BCKDK, antagonizing TRIM21-mediated proteasomal degradation, thereby stabilizing BCKDK and promoting SLC7A5/SLC7A8-mediated branched-chain amino acid (BCAA) uptake by GBM cells, leading to NK cell BCAA depletion and immune suppression. Co-immunoprecipitation, ubiquitination assays, PSMD14 knockdown/pharmacological inhibition (OPA), NK cytotoxicity assays, preclinical GBM models Cell Death & Differentiation Medium 41876842
2025 PSMD14 stabilizes IMPDH2, the rate-limiting enzyme of purine nucleotide biosynthesis, by selectively removing K48-linked polyubiquitin chains. PSMD14 inhibition decreases IMPDH2 stability, impairs nucleotide metabolism, causes mitochondrial dysfunction, and increases DNA damage signaling in GBM. Exogenous guanosine reverses these effects. Immunoprecipitation-coupled mass spectrometry (IP-MS), K48-specific ubiquitination assays, metabolic assays, mitochondrial function assessments, guanosine rescue experiments, orthotopic GBM mouse models Theranostics Medium 41608571
2025 PSMD14 stabilizes PD-L1 by interacting with its intracellular domain and removing K48-linked polyubiquitin chains, thereby inhibiting proteasomal degradation of PD-L1. PSMD14 inhibition promotes PD-L1 degradation, enhances CD8+ T cell activation, reduces Tregs and MDSCs, and improves immunotherapy response in breast cancer syngeneic models. Co-immunoprecipitation, K48-specific ubiquitination assay, cycloheximide chase assay, flow cytometry, T cell cytotoxicity assay, syngeneic mouse models Journal of Experimental & Clinical Cancer Research Medium 41981629
2025 PSMD14 deubiquitinates SF3B4 (K63-linked ubiquitin removal), stabilizing SF3B4, which then forms a complex with HNRNPC to promote exon inclusion in FADS1 mRNA via m6A-HNRNPC recognition, upregulating FADS1 and activating Akt/mTOR signaling in TNBC. Co-IP, K63-specific deubiquitination assays, RNA splicing analysis, m6A-RIP, TNBC organoid (PDO) and PDX models Science Advances Medium 40344056
2025 TXNL1's C-terminal tail covers the catalytic groove of the Rpn11 deubiquitinase and coordinates the active-site Zn2+ specifically in substrate-degrading proteasome conformational states (but not in resting state), as revealed by time-resolved cryo-EM. This is consistent with TXNL1 binding to the actively processing proteasome and potentially modulating Rpn11 activity. Time-resolved cryo-EM at saturating and sub-stoichiometric TXNL1 concentrations, biophysical binding experiments bioRxiv (preprint)preprint Medium bio_10.1101_2024.11.08.622731
2025 PSMD14/Rpn11 functions non-enzymatically as a receptor for the midnolin ubiquitin-like (Ubl) domain in the midnolin-proteasome pathway (ubiquitin-independent degradation). Cryo-EM structures of the MIDN-bound proteasome show the midnolin Ubl domain binding to Rpn11 (not cleaved by it), positioning the substrate-binding Catch domain above the proteasomal channel. This is distinct from Rpn11's canonical deubiquitinase function. Cryo-EM structures of MIDN-bound human proteasome in two conformational states bioRxiv (preprint)preprint Medium bio_10.1101_2025.02.22.639686
2025 In the ubiquitin-independent ODC degradation pathway, Rpn11's JAMM motif guides the ODC C-tail into the AAA+ ATPase ring, acting as a translocation gateway and repurposing Rpn11 for a novel ubiquitin-independent function distinct from its canonical deubiquitinase role. Cryo-EM (eleven structures of human 26S proteasome-ODC complexes capturing full degradation process), mutagenesis bioRxiv (preprint)preprint Medium bio_10.1101_2025.11.15.688597
2025 PSMD14 deubiquitinates CARM1 (coactivator-associated arginine methyltransferase 1), stabilizing it. Stabilized CARM1 activates transcription of FERMT1 through H3R17 dimethylation, promoting HCC proliferation and metastasis. Co-immunoprecipitation, ubiquitination assays, ChIP assay, in vitro and in vivo cell proliferation/metastasis models Cell Death & Disease Medium 40016178
2025 PSMD14 deubiquitinates RBM15B, preventing its ubiquitin-mediated degradation. Stabilized RBM15B promotes m6A modification of SPON2 mRNA and its stability, facilitating pancreatic cancer progression. PSMD14 itself is transcriptionally activated by MEF2A. ChIP assay (MEF2A-PSMD14 promoter), dual luciferase, co-immunoprecipitation, ubiquitination assay, RIP assay (RBM15B-SPON2 mRNA), MeRIP (m6A on SPON2), subcutaneous and lung metastasis mouse models Kaohsiung Journal of Medical Sciences Medium 40066751
2025 PSMD14 deubiquitinates PFKFB2 at K355, facilitating SCYL2-mediated phosphorylation of PFKFB2, which increases fructose-2,6-bisphosphate generation, activates PFK1, and promotes glycolysis and H3K27 lactylation in gastric adenocarcinoma. H3K27 lactylation in turn activates PSMD14 and SOX9 expression, forming a positive feedback loop. Co-immunoprecipitation, site-specific ubiquitination assay (K355), phosphorylation assays, glycolysis metabolic assays, H3K27 lactylation ChIP, FDA drug screening for PSMD14 inhibitors Cell Death & Differentiation Medium 41193870
2025 PSMD14 stabilizes FOXM1 by reducing K63-linked ubiquitination on FOXM1, promoting breast cancer progression. PSMD14 also activates the PI3K/AKT/mTOR pathway. Co-immunoprecipitation, immunofluorescence, K63-specific in vitro and in vivo deubiquitination assays, xenograft mouse model International Journal of Biological Macromolecules Medium 40902741
2025 PSMD14 deubiquitinates and stabilizes CDC42 in endothelial cells, promoting filopodia formation and cell migration. Silencing PSMD14 impairs filopodia formation, migration, and CDC42 stability. Co-immunoprecipitation (PSMD14-CDC42 interaction), CDC42 stability/ubiquitination assays, siRNA knockdown, filopodia imaging, migration assays, mouse hindlimb ischemia model Angiogenesis Medium 40833626
2025 Histone lactylation (H3K18la) upregulates PSMD14 transcription after traumatic brain injury. PSMD14 then deubiquitinates PKM2, maintaining PKM protein stability and enabling PSMD14-mediated mitophagy via PINK1 phosphorylation at Thr257, thereby suppressing neuron PANoptosis. LC-MS proteomic analysis, co-immunoprecipitation, ubiquitination assays, PINK1 phosphorylation assays, mitophagy flux analysis, controlled cortical impact (CCI) mouse model Autophagy Medium 40000916
2026 DUSP4-mediated dephosphorylation of PSMD14 enhances PSMD14's interaction with MICALL2 and its deubiquitination activity toward MICALL2, stabilizing MICALL2 and promoting ccRCC malignant progression. Co-immunoprecipitation, MICALL2 ubiquitination assay, PSMD14 phosphorylation analysis, siRNA knockdown, in vivo ccRCC mouse model Journal of Translational Medicine Medium 42174657

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science (New York, N.Y.) 852 12183636
2009 K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1. The EMBO journal 194 19214193
2002 MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function. BMC biochemistry 181 12370088
2012 The proteasomal de-ubiquitinating enzyme POH1 promotes the double-strand DNA break response. The EMBO journal 136 22909820
2014 Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate deubiquitination during proteasomal degradation. Nature structural & molecular biology 133 24463465
2017 Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11. Nature chemical biology 129 28244987
2003 Complementary roles for Rpn11 and Ubp6 in deubiquitination and proteolysis by the proteasome. The Journal of biological chemistry 121 14581483
2014 Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11. Proceedings of the National Academy of Sciences of the United States of America 114 24516147
2017 Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases. Nature chemical biology 110 28459440
2015 POH1 deubiquitylates and stabilizes E2F1 to promote tumour formation. Nature communications 98 26510456
2013 Co-operation of BRCA1 and POH1 relieves the barriers posed by 53BP1 and RAP80 to resection. Nucleic acids research 97 24013561
2019 Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2. Cancer letters 93 31634528
2019 ECT2/PSMD14/PTTG1 axis promotes the proliferation of glioma through stabilizing E2F1. Neuro-oncology 92 30590814
2017 An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome. Molecular cell 87 28844860
2017 Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Oncogene 83 28581522
2018 Deubiquitinating enzyme PSMD14 promotes tumor metastasis through stabilizing SNAIL in human esophageal squamous cell carcinoma. Cancer letters 72 29331416
1998 A mutation in a novel yeast proteasomal gene, RPN11/MPR1, produces a cell cycle arrest, overreplication of nuclear and mitochondrial DNA, and an altered mitochondrial morphology. Molecular biology of the cell 68 9763452
2021 Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2. Molecular oncology 60 34382324
2007 The JAMM motif of human deubiquitinase Poh1 is essential for cell viability. Molecular cancer therapeutics 60 17237285
2021 Blockade of deubiquitinating enzyme PSMD14 overcomes chemoresistance in head and neck squamous cell carcinoma by antagonizing E2F1/Akt/SOX2-mediated stemness. Theranostics 59 33456565
2021 The PSMD14 inhibitor Thiolutin as a novel therapeutic approach for esophageal squamous cell carcinoma through facilitating SNAIL degradation. Theranostics 56 33897885
2009 Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence. Experimental cell research 54 19732767
2004 Participation of the proteasomal lid subunit Rpn11 in mitochondrial morphology and function is mapped to a distinct C-terminal domain. The Biochemical journal 50 15018611
2019 The deubiquitinating enzyme PSMD14 facilitates tumor growth and chemoresistance through stabilizing the ALK2 receptor in the initiation of BMP6 signaling pathway. EBioMedicine 47 31685442
2006 The 19 S proteasomal subunit POH1 contributes to the regulation of c-Jun ubiquitination, stability, and subcellular localization. The Journal of biological chemistry 41 16569633
2009 Regulation of ErbB2 receptor status by the proteasomal DUB POH1. PloS one 39 19436748
2019 POH1 contributes to hyperactivation of TGF-β signaling and facilitates hepatocellular carcinoma metastasis through deubiquitinating TGF-β receptors and caveolin-1. EBioMedicine 38 30745168
2018 Epidithiodiketopiperazines Inhibit Protein Degradation by Targeting Proteasome Deubiquitinase Rpn11. Cell chemical biology 38 30146242
2018 POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity. Nature communications 37 30315153
2014 Disassembly of Lys11 and mixed linkage polyubiquitin conjugates provides insights into function of proteasomal deubiquitinases Rpn11 and Ubp6. The Journal of biological chemistry 37 25389291
2008 Dissection of the carboxyl-terminal domain of the proteasomal subunit Rpn11 in maintenance of mitochondrial structure and function. Molecular biology of the cell 35 18172023
2025 Histone lactylation stimulated upregulation of PSMD14 alleviates neuron PANoptosis through deubiquitinating PKM2 to activate PINK1-mediated mitophagy after traumatic brain injury. Autophagy 34 40000916
2017 RPN11 deubiquitinase promotes proliferation and migration of breast cancer cells. Molecular medicine reports 33 28535005
2023 The proteasome component PSMD14 drives myelomagenesis through a histone deubiquitinase activity. Molecular cell 32 37935198
2018 POH1 Knockdown Induces Cancer Cell Apoptosis via p53 and Bim. Neoplasia (New York, N.Y.) 32 29573636
2023 PSMD14 stabilizes estrogen signaling and facilitates breast cancer progression via deubiquitinating ERα. Oncogene 30 38017133
2010 The 19S proteasomal lid subunit POH1 enhances the transcriptional activation by Mitf in osteoclasts. Journal of cellular biochemistry 29 20058232
2024 Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11. Cell metabolism 28 39146936
2013 Integrity of the Saccharomyces cerevisiae Rpn11 protein is critical for formation of proteasome storage granules (PSG) and survival in stationary phase. PloS one 26 23936414
2022 Deubiquitylase PSMD14 inhibits autophagy to promote ovarian cancer progression via stabilization of LRPPRC. Biochimica et biophysica acta. Molecular basis of disease 24 36328147
2018 Rpn11-mediated ubiquitin processing in an ancestral archaeal ubiquitination system. Nature communications 24 30002364
2002 Mitochondrial effects of the pleiotropic proteasomal mutation mpr1/rpn11: uncoupling from cell cycle defects in extragenic revertants. Gene 24 11943459
2022 PSMD14 Targeting Triggers Paraptosis in Breast Cancer Cells by Inducing Proteasome Inhibition and Ca2+ Imbalance. International journal of molecular sciences 23 35269789
2002 The essential 26S proteasome subunit Rpn11 confers multidrug resistance to mammalian cells. Anticancer research 22 12553011
2022 Novel insights into the non-canonical roles of PSMD14/POH1/Rpn11 in proteostasis and in the modulation of cancer progression. Cellular signalling 20 36241058
2019 Targeting POH1 inhibits prostate cancer cell growth and enhances the suppressive efficacy of androgen deprivation and docetaxel. The Prostate 20 31212367
2022 Deubiquitinating enzyme PSMD14 facilitates gastric carcinogenesis through stabilizing PTBP1. Experimental cell research 17 35405117
2014 The proteasomal Rpn11 metalloprotease suppresses tombusvirus RNA recombination and promotes viral replication via facilitating assembly of the viral replicase complex. Journal of virology 17 25540361
2011 A proteasome assembly defect in rpn3 mutants is associated with Rpn11 instability and increased sensitivity to stress. Journal of molecular biology 17 21619884
2020 Targeting PSMD14 inhibits melanoma growth through SMAD3 stabilization. Scientific reports 16 33154524
2020 The Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-to-ER Retrograde Transport. Cells 15 32210007
2023 POH1 induces Smad3 deubiquitination and promotes lung cancer metastasis. Cancer letters 14 38061486
2018 Requirement for POH1 in differentiation and maintenance of regulatory T cells. Cell death and differentiation 14 30038387
2018 Computational Studies on the Inhibitor Selectivity of Human JAMM Deubiquitinylases Rpn11 and CSN5. Frontiers in chemistry 14 30356695
2025 PSMD14 Stabilizes SLC7A11 to Ameliorate Glucocorticoid-Induced Osteoporosis by Suppressing Osteocyte Ferroptosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 40444470
2021 A novel viral strategy for host factor recruitment: The co-opted proteasomal Rpn11 protein interaction hub in cooperation with subverted actin filaments are targeted to deliver cytosolic host factors for viral replication. PLoS pathogens 11 34161398
2010 Synthetic lethality of rpn11-1 rpn10Δ is linked to altered proteasome assembly and activity. Current genetics 11 20941496
2025 ALKBH1 knockdown promotes the growth, migration and invasion of HTR-8/SVneo cells through regulating the m5C modification PSMD14. Scientific reports 10 40025166
2025 Targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 m6A modification in triple-negative breast cancer. Science advances 10 40344056
2023 Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4. PeerJ 10 36632137
2022 Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle. International journal of molecular sciences 10 35328679
2025 The deubiquitinase Rpn11 functions as an allosteric ubiquitin sensor to promote substrate engagement by the 26S proteasome. Cell reports 8 40411784
2023 The function and mechanism of PSMD14 in promoting progression and resistance to anlotinib in osteosarcoma. Cancer cell international 8 38053170
2025 PSMD14-mediated deubiquitination of CARM1 facilitates the proliferation and metastasis of hepatocellular carcinoma by inducing the transcriptional activation of FERMT1. Cell death & disease 7 40016178
2024 An LRPPRC-HAPSTR1-PSMD14 interaction regulates tumor progression in ovarian cancer. Aging 7 38643468
2024 Deubiquitinase PSMD14 promotes tumorigenicity of glioblastoma by deubiquitinating and stabilizing β-catenin. BioFactors (Oxford, England) 7 38696072
2023 POH1 facilitates pancreatic carcinogenesis through MYC-driven acinar-to-ductal metaplasia and is a potential therapeutic target. Cancer letters 7 37844756
2010 Analysis of the rpn11-m1 proteasomal mutant reveals connection between cell cycle and mitochondrial biogenesis. FEMS yeast research 6 21059189
2025 PSMD14 Transcriptionally Activated by MEF2A Promotes Pancreatic Cancer Development by Upregulating SPON2 Expression. The Kaohsiung journal of medical sciences 5 40066751
2025 PSMD14/E2F1 Axis-Mediated CENPF Promotes the Metastasis of Triple-Negative Breast Cancer Through Inhibiting Ferroptosis. Cancer science 4 40365861
2025 PSMD14 promotes breast cancer progression by reducing K63-linked ubiquitination on FOXM1 and activating the PI3K/AKT/mTOR pathway. International journal of biological macromolecules 4 40902741
2025 PSMD14-Mediated LDHA Deubiquitination Upregulates ACLY Expression via H3K18 Lactylation to Promote Lipid Synthesis and Pancreatic Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 41051446
2020 Transient Breakage of the Nucleocytoplasmic Barrier Controls Spore Maturation via Mobilizing the Proteasome Subunit Rpn11 in the Fission Yeast Schizosaccharomyces pombe. Journal of fungi (Basel, Switzerland) 4 33113963
2018 New perspectives on Mega plasmid sequence (poh1) in Bacillus thuringiensis ATCC 10792 harbouring antimicrobial, insecticidal and antibiotic resistance genes. Microbial pathogenesis 4 30326263
2025 Design and synthesis of thiolutin derived PSMD14/HDAC dual-target inhibitors against esophageal squamous cell carcinoma. Bioorganic chemistry 3 40311241
2023 High-Throughput Assay for Characterizing Rpn11 Deubiquitinase Activity. Methods in molecular biology (Clifton, N.J.) 3 36350544
2023 Regulation of Drp1 and enhancement of mitochondrial fission by the deubiquitinating enzyme PSMD14 facilitates the proliferation of bladder cancer cells. Oncology reports 3 37975230
2025 PSMD14-mediated PFKFB2 deubiquitination activates H3K27 lactylation to drive cancer stemness in gastric adenocarcinoma. Cell death and differentiation 2 41193870
2021 An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity. Biomolecules 2 34572530
2025 Blocking PSMD14-mediated E2F1/ERK/AKT signaling pathways suppresses the progression of anaplastic thyroid cancer. Cellular signalling 1 40262717
2025 MY-1 promotes angiogenesis in the ischemic hindlimbs by regulating the stability of CDC42 via PSMD14. Angiogenesis 1 40833626
2025 PSMD14 drives lung adenocarcinoma progression through HMMR stabilization and dual activation of TGF-β/Smad and PI3K/AKT/mTOR signaling. Frontiers in immunology 1 41488674
2014 [Design of cell line stable expressing proteasomal subunit PSMD14 fused to the fluorescent protein EGFP and HTBH tag based on HEK293 cells]. Tsitologiia 1 25509418
2026 Coupling proteostasis and de novo purine biosynthesis of PSMD14 fuels glioblastoma progression and chemoresistance. Theranostics 0 41608571
2026 Covalent targeting of PSMD14 by Eupalinolide B induces oncoprotein degradation and apoptosis in acute promyelocytic leukemia cells. RSC chemical biology 0 41647277
2026 Ethyl ferulate suppresses choroidal neovascularization by accelerating Keap1 degradation through the inhibition of PSMD14-mediated deubiquitination. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41650523
2026 Targeting the PSMD14-BCKDK pathway overcomes immune suppression and enhances CAR-NK infiltration in glioblastoma. Cell death and differentiation 0 41876842
2026 Targeting PSMD14 enhances immunotherapy efficacy by promoting PD-L1 degradation and reshaping the tumor microenvironment in breast cancer. Journal of experimental & clinical cancer research : CR 0 41981629
2026 DUSP4-mediated dephosphorylation of PSMD14 enhances PSMD14-dependent deubiquitination of MICALL2 and promotes malignant progression in clear cell renal cell carcinoma. Journal of translational medicine 0 42174657
2024 The deubiquitinase Rpn11 functions as an allosteric ubiquitin sensor to promote substrate engagement by the 26S proteasome. bioRxiv : the preprint server for biology 0 39484543

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