Affinage

USP14

Ubiquitin carboxyl-terminal hydrolase 14 · UniProt P54578

Length
494 aa
Mass
56.1 kDa
Annotated
2026-06-10
100 papers in source corpus 53 papers cited in narrative 53 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP14 is a proteasome-associated cysteine deubiquitinase that controls the entry of ubiquitinated substrates into the 26S proteasome and broadly stabilizes specific cellular proteins by removing their ubiquitin chains (PMID:9344467, PMID:14581483, PMID:27074503). Its catalytic domain is held in an autoinhibited state by two surface loops (BL1/BL2) that occlude the active site until ubiquitin binding displaces them, positioning the ubiquitin C-terminus for hydrolysis (PMID:16211010). USP14 docks onto the 19S regulatory particle base via its N-terminal UBL domain, which binds Rpn1, while its catalytic USP domain bridges Rpn1 and Rpt1 and is positioned near the ATPase ring mouth and Rpn11 upon ubiquitin engagement (PMID:26130806, PMID:35149681). Functionally it acts on two registers: in the absence of substrate it allosterically inhibits proteasome peptidase, ATPase, and Rpn11 activities through a noncatalytic mechanism, whereas upon engaging multi-site ubiquitinated substrates it removes chains en bloc on a millisecond timescale, reducing substrate dwell time and rejecting substrates before degradation commits (PMID:17018280, PMID:27074503, PMID:28416611); time-resolved cryo-EM shows ubiquitin-dependent USP14 activation reprograms the ATPase motor, stimulates gate opening, and imposes regulatory checkpoints during translocation (PMID:35477760). Both the activating and inhibitory functions converge on the same Rpt1-binding interface (the ILR element within BL1), mechanistically linking catalysis and allosteric inhibition (PMID:35149681). USP14 also recycles ubiquitin to maintain cellular free ubiquitin pools, loss of which causes neuromuscular junction and synaptic transmission defects in mice (PMID:14559899, PMID:16190881, PMID:19726649), and it independently controls synaptic vesicle number and short-term plasticity through a catalysis-independent function (PMID:12368914, PMID:24218545). Beyond the proteasome, USP14 stabilizes diverse substrates by direct deubiquitination — including the androgen receptor, FASN, IDO1, TAZ, and Ku70 — and regulates Wnt/Dishevelled and RIG-I antiviral signaling, with roles spanning DNA repair, metabolism, immunity, and cancer (PMID:27074503, PMID:29353883, PMID:30425250, PMID:31740976, PMID:30466171, PMID:35906484).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Establishing whether the USP14 ortholog is itself a functional protease defined the gene as a ubiquitin-specific cysteine protease rather than a structural adaptor.

    Evidence in vitro enzymatic assays with purified yeast Ubp6 and radiolabeled ubiquitin substrates

    PMID:9344467

    Open questions at the time
    • Did not place the enzyme at the proteasome
    • Chain-length and linkage preferences not yet resolved
  2. 2002 High

    Linking USP14 loss to a defined physiological phenotype showed the enzyme regulates synaptic transmission in vivo, separating its organismal role from gross protein turnover.

    Evidence positional cloning, in vitro deubiquitination, and electrophysiology in ax(J) mice

    PMID:12368914

    Open questions at the time
    • Reported inability to process polyubiquitin chains conflicted with later proteasome-context findings
    • Molecular target at the synapse unknown
  3. 2003 High

    Positioning Ubp6 in the proteasome base and showing it maintains free ubiquitin pools defined USP14 as a proteasome-associated DUB acting alongside Rpn11.

    Evidence proteasome purification from deletion mutants, genetic double-mutant lethality, fluorescence localization, and ubiquitin-overexpression suppression in yeast

    PMID:14559899 PMID:14581483

    Open questions at the time
    • Mechanism distinguishing Ubp6 and Rpn11 deubiquitination not yet defined
    • Structural basis of proteasome docking unresolved
  4. 2005 High

    Atomic structures revealed how USP14 catalysis is gated, explaining ubiquitin-induced activation, while mammalian fractionation confirmed conservation of its ubiquitin-recycling role.

    Evidence X-ray crystallography of free enzyme and ubiquitin-aldehyde complex; proteasome co-fractionation and free-ubiquitin quantitation in ax(J) mice

    PMID:16190881 PMID:16211010

    Open questions at the time
    • Structures of the full proteasome-bound enzyme not yet available
    • Did not address allosteric effects on the proteasome
  5. 2006 High

    Distinguishing catalytic from noncatalytic activity showed USP14 can delay degradation independent of deubiquitination, revealing a dual-mode regulator of the proteasome.

    Evidence in vitro and cell-based degradation assays with catalytic-dead Ubp6 and comparison to Rpn11

    PMID:17018280

    Open questions at the time
    • Structural basis of noncatalytic inhibition undefined
    • Physiological substrates of the timing effect unknown
  6. 2011 High

    Demonstrating a role in 19S assembly added a developmental dimension to USP14 beyond steady-state regulation.

    Evidence native mass spectrometry of intact proteasomes and ubp6/hsm3 genetic epistasis in yeast

    PMID:21658604

    Open questions at the time
    • Whether the assembly role is conserved in mammals not tested here
    • Catalytic vs noncatalytic contribution to assembly not fully separated
  7. 2014 High

    Defining chain-type and chain-length preferences clarified how USP14 cleaves polyubiquitin differently from Rpn11 and how proteasome incorporation boosts overall deconjugation.

    Evidence in vitro kinetic deubiquitination assays with defined homo- and heterogeneous polyubiquitin conjugates

    PMID:25389291

    Open questions at the time
    • Behavior on physiological multi-chain substrates not directly addressed
    • Single-molecule kinetics on the proteasome not measured here
  8. 2016 High

    Showing preference for multi-site ubiquitinated substrates with en bloc, millisecond chain removal established USP14's substrate-rejection role as a degradation checkpoint.

    Evidence in vitro reconstitution with defined cyclin B conjugates and single-molecule fluorescence, with yeast-human conservation tests

    PMID:27074503

    Open questions at the time
    • Structural intermediates during chain removal not captured
    • How rejection is coordinated with translocation unresolved
  9. 2015 High

    Cryo-EM placed the UBL on Rpn1 and the USP domain bridging Rpn1-Rpt1, explaining how USP14 binding drives a kinetically distinct proteasome conformation.

    Evidence single-particle cryo-EM with cross-linking mass spectrometry of yeast proteasome-Ubp6

    PMID:26130806

    Open questions at the time
    • Conformational dynamics during active substrate processing not resolved at this stage
    • Activation interface not yet mutationally mapped
  10. 2017 High

    Quantifying allosteric inhibition of multiple proteasome activities and substrate-driven recruitment cycling defined USP14 as a substrate-gated brake on the proteasome.

    Evidence enzymatic comparison of Usp14-knockout vs wild-type proteasomes with catalytic-dead reconstitution; native co-IP and recombinant-protein binding with inhibitor experiments

    PMID:28396413 PMID:28416611

    Open questions at the time
    • The interface responsible for noncatalytic inhibition not yet identified
    • Co-cycling with Ube3c functionally underexplored
  11. 2018 High

    Isolating the UBL domain showed it alone stimulates the very activities full-length USP14 inhibits, dissecting domain-specific opposing effects on the proteasome.

    Evidence addition of purified isolated UBL domain to 26S proteasomes with multiple enzymatic and cell-based degradation assays

    PMID:30487212

    Open questions at the time
    • How the catalytic domain overrides UBL stimulation in the full enzyme not fully resolved
    • In vivo relevance of UBL-only stimulation unclear
  12. 2018 Medium

    Identifying direct substrates (AR, FASN) and a regulator (TRIM11) extended USP14 from a proteasome modulator to a stabilizer of disease-relevant proteins.

    Evidence Co-IP, ubiquitination assays, cycloheximide chase, and in vivo mouse metabolic and oncologic models

    PMID:29353883 PMID:29581427 PMID:30425250

    Open questions at the time
    • Direct vs proteasome-context deubiquitination not always disentangled
    • Reciprocal validation of some interactions limited to single labs
  13. 2020 Medium

    Comparing inactive USP14 and UCHL5 mutants demonstrated substrate selectivity among proteasome-associated DUBs and identified accumulating targets including beta-catenin.

    Evidence expression of catalytically dead USP14 C114A, ubiquitin immunoprecipitation, and mass spectrometry

    PMID:31703099

    Open questions at the time
    • Mechanistic basis for DUB substrate selectivity unresolved
    • Direct vs indirect substrate accumulation not fully separated
  14. 2022 High

    High-resolution time-resolved cryo-EM and ILR-element mutagenesis revealed how ubiquitin-dependent activation reprograms the ATPase motor and mechanistically links activation with noncatalytic inhibition.

    Evidence time-resolved single-particle cryo-EM across 13 proteasome states; cryo-EM with site-directed mutagenesis of the Ubp6 ILR element and Rpt1

    PMID:35149681 PMID:35477760

    Open questions at the time
    • How the three checkpoints are regulated in cells not established
    • Whether human-specific regulators modulate these states unknown
  15. 2023 Medium

    A broad panel of substrate-stabilization studies (IDO1, TAZ, Ku70, RIG-I, NLRP3 and others) mapped USP14's reach into immunity, DNA repair, signaling, and metabolism.

    Evidence Co-IP, linkage-specific ubiquitination assays, and in vivo tumor, immune, and metabolic models across multiple labs

    PMID:30466171 PMID:31740976 PMID:35906484 PMID:36163134 PMID:37055579 PMID:37633951

    Open questions at the time
    • Many substrates rest on single-lab Co-IP/ubiquitination assays without reciprocal or structural validation
    • Whether stabilization occurs at the proteasome or independently is often unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP14's proteasome-gating function is integrated with its many reported free-standing substrate-stabilization roles, and which of those substrates reflect direct catalysis versus proteasome-context effects, remains unresolved.
  • No unifying framework distinguishing on-proteasome vs off-proteasome deubiquitination
  • Most disease substrates lack structural or reconstituted-enzyme confirmation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0098772 molecular function regulator activity 4 GO:0016787 hydrolase activity 3 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 3 R-HSA-73894 DNA Repair 2 R-HSA-8953854 Metabolism of RNA 2
Partners
HSC70IRE1ARELARNF168RPN1RPN11RPT1TRIM11
Complex memberships
19S regulatory particle26S proteasome

Evidence

Reading pass · 53 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Crystal structures of USP14 catalytic domain alone and in complex with ubiquitin aldehyde revealed that, in the absence of ubiquitin, the active site is blocked by two surface loops (BL1 and BL2); ubiquitin binding induces a conformational change that relocates these loops, allowing the ubiquitin C-terminus to access the active site, explaining how USP14 is catalytically activated. X-ray crystallography (free enzyme and ubiquitin aldehyde complex) combined with biochemical characterization The EMBO journal High 16211010
1997 Purified yeast Ubp6 (USP14 ortholog) is a cysteine protease that hydrolyzes ubiquitin-protein fusions and can release ubiquitin from branched polyubiquitin-protein conjugates, and its activity is blocked by sulfhydryl-blocking reagents and ubiquitin aldehyde. Biochemical purification from E. coli and in vitro enzymatic assays with radiolabeled ubiquitin substrates Archives of biochemistry and biophysics High 9344467
2003 Yeast Ubp6 (USP14 ortholog) is situated in the base subcomplex of the 26S proteasome, and both Ubp6 and Rpn11 serve complementary but distinct deubiquitinating roles on the proteasome; loss of either slows deubiquitination and the double mutant is synthetically lethal. Purification of proteasomes from rpn11 and ubp6 deletion mutants; in vitro deubiquitination assays; genetic double-mutant lethality The Journal of biological chemistry High 14581483
2003 Loss of yeast Ubp6 depletes the free ubiquitin pool because Ubp6 recycles ubiquitin at the proteasome; overexpression of ubiquitin suppresses all ubp6Δ defects. Human USP14 fully complements ubp6Δ and binds the yeast proteasome via its N-terminal UBL domain, which targets it to the proteasome but is not required for nuclear localization. Genetic complementation assays in yeast, fluorescence microscopy (Ubp6-GFP localization), ubiquitin-overexpression suppression experiments The Journal of biological chemistry High 14559899
2002 Usp14 (ax gene product) is a cysteine protease that cleaves ubiquitin-tagged protein substrates in vitro but cannot process polyubiquitin chains; loss-of-function in ax(J) mice causes synaptic transmission defects in central and peripheral nervous systems without neuronal loss or protein aggregates, indicating a role in regulating synaptic activity via ubiquitin processing. Positional cloning; in vitro deubiquitination assays; electrophysiology in ax(J) mice Nature genetics High 12368914
2005 Usp14 co-fractionates with proteasomes isolated from mouse liver and brain; loss of Usp14 in ax(J) mice reduces monomeric ubiquitin levels ~35% in most tissues, demonstrating that Usp14 functions to maintain cellular free ubiquitin pools in mammals. Subcellular fractionation/co-fractionation with proteasomes; quantitative immunoblotting of free ubiquitin in ax(J) tissues Journal of neurochemistry High 16190881
2006 Yeast Ubp6 (USP14 ortholog) can delay proteasomal degradation of ubiquitinated proteins through a noncatalytic, proteasome-inhibitory function independent of its deubiquitinating activity; it also gradually deubiquitinates substrates over time, creating a switch in ubiquitin chain processing mode from en bloc removal (by Rpn11) to stepwise trimming. In vitro and cell-based degradation assays using catalytic-dead Ubp6 mutants; pulse-chase experiments; comparison with Rpn11 activity Cell High 17018280
2009 USP14 interacts with the cytoplasmic region of IRE1α; USP14 overexpression inhibits ER-associated degradation (ERAD), and USP14 knockdown activates ERAD, identifying USP14 as a physiological inhibitor of ERAD under non-stressed conditions. Co-immunoprecipitation; siRNA knockdown; ERAD activity assays Biochemical and biophysical research communications Medium 19135427
2009 Usp14 is indispensable for synaptic development and function at neuromuscular junctions (NMJs); Usp14-deficient mice show presynaptic phosphorylated neurofilament accumulations, nerve terminal sprouting, and postsynaptic acetylcholine receptor immaturity. The greatest ubiquitin depletion occurred in synaptosomal fractions. Transgenic restoration of Usp14 in neurons corrected ubiquitin levels and NMJ defects. Genetic rescue (transgenic neuron-specific Usp14 re-expression in ax(J) mice); immunofluorescence; synaptosomal fractionation; electrophysiology The Journal of neuroscience High 19726649
2011 The catalytic activity of Ubp6 (USP14 ortholog) is required for maturation of the 26S proteasome 19S regulatory particle; Ubp6 is an additional member of the Hsm3 chaperone module, and genetic interactions show functional overlap with Hsm3 but not other RP chaperones. Ubp6 facilitates assembly by clearing ubiquitylated substrates from assembly precursors. Quantitative proteomics and native mass spectrometry of intact proteasome complexes; genetic interaction analysis (ubp6/hsm3 double deletions) Molecular cell High 21658604
2013 USP14 mediates deubiquitination of Dishevelled (Dvl) at K63-linked polyubiquitin chains, and genetic or chemical suppression of USP14 increases Dvl polyubiquitination and impairs downstream Wnt/β-catenin signaling, placing USP14 as a positive regulator of canonical Wnt signaling. siRNA screen; Co-immunoprecipitation; ubiquitin chain-type analysis; chemical inhibitor experiments; Wnt reporter assays Oncogenesis Medium 23958854
2013 USP14 regulates hippocampal synaptic short-term plasticity and synaptic vesicle number through a deubiquitination-independent mechanism; overexpression of catalytically inactive USP14 rescues paired-pulse facilitation deficits and restores vesicle number in Usp14-deficient neurons, and the PPF deficit is also rescued by proteasome inhibition. Electrophysiology (paired-pulse facilitation); electron microscopy (synaptic vesicle counting); catalytic-dead USP14 overexpression rescue; pharmacological proteasome inhibition The Journal of physiology High 24218545
2015 Cryo-EM combined with cross-linking/MS showed that Ubp6 binds the proteasome via its N-terminal UBL domain to Rpn1, while its catalytic USP domain is variably positioned. In the presence of ubiquitin aldehyde, the USP domain is stabilized bridging Rpn1 and Rpt1, with the active site positioned near the ATPase ring mouth and Rpn11. Ubp6 binding drives the proteasome into an intermediate conformational state, explaining kinetic effects on degradation. Single-particle cryo-EM; cross-linking mass spectrometry; proteasome conformational state analysis Proceedings of the National Academy of Sciences of the United States of America High 26130806
2016 USP14 shows marked preference for substrates bearing multiple ubiquitin modifications or chains (multi-site ubiquitinated substrates) independent of chain linkage type, removing chains en bloc until a single chain remains. This specificity is conserved from yeast to humans. Single-molecule studies showed USP14-dependent deubiquitination reduces dwell time of ubiquitin conjugates at the proteasome, acting on a millisecond timescale to reject substrates before degradation initiates. In vitro deubiquitination assays with defined ubiquitin-cyclin B conjugates; single-molecule fluorescence; yeast–human conservation experiments Nature High 27074503
2017 USP14 allosterically inhibits multiple 26S proteasome activities (peptidase, ATPase, Rpn11-dependent deubiquitination) in the absence of ubiquitinated substrates; a catalytically inactive USP14 mutant retains this inhibitory activity, confirming it is noncatalytic. Proteasomes lacking Usp14 show elevated basal peptidase activity, enhanced ATPase activity, and are able to degrade non-ubiquitinated proteins at much higher rates. Biochemical comparison of proteasomes purified from Usp14-knockout vs. wild-type MEFs; addition of purified catalytic-dead Usp14 mutant; multiple enzymatic activity assays The Journal of biological chemistry High 28416611
2017 Ubiquitinated proteins promote association of both Usp14 and Ube3c with 26S proteasomes; when ubiquitin conjugates are hydrolyzed or ubiquitination is prevented, Usp14 and Ube3c rapidly dissociate. Recombinant Usp14 binds purified proteasomes preferentially when they contain ubiquitin conjugates, and inhibitors (IU-1 or ubiquitin aldehyde) enhance binding. Usp14 and Ube3c cycle on/off together in a substrate-dependent manner. Native co-immunoprecipitation from cell extracts; addition of recombinant Usp14 to purified proteasomes; small molecule inhibitor experiments; quantitative immunoblotting Proceedings of the National Academy of Sciences of the United States of America High 28396413
2018 The UBL domain of Usp14 alone, when added to purified 26S proteasomes, stimulates the same activities that full-length Usp14 inhibits (peptide entry/hydrolysis, protein-dependent ATPase, Rpn11 deubiquitination, and degradation of both ubiquitinated and non-ubiquitinated proteins), apparently by binding Rpn1's T2 site to allosterically activate the proteasome. Biochemical assay of isolated UBL domain added to purified 26S proteasomes; comparison with Usp14-knockout proteasomes; cell-based protein degradation assays using UBL-domain expression Proceedings of the National Academy of Sciences of the United States of America High 30487212
2018 USP14 directly interacts with and deubiquitinates androgen receptor (AR), stabilizing AR protein by removing its ubiquitin chain. Inhibition or knockdown of USP14 accelerates K48-linked ubiquitination and proteasome-mediated degradation of AR in breast cancer cells. Co-immunoprecipitation; ubiquitination assays; cycloheximide chase; pharmacological and siRNA inhibition of USP14 Oncogene Medium 29353883
2018 USP14 interacts with RNF168 (via RNF168's MIU1 domain) and directly deubiquitinates it in vitro; USP14 is itself a substrate of autophagy (interacting with MAP1LC3B and the UBA domain of SQSTM1/p62). USP14 antagonizes RNF168-dependent ubiquitin signaling and downstream 53BP1 chromatin recruitment at DNA double-strand breaks. Co-immunoprecipitation; colocalization by immunofluorescence; in vitro deubiquitination assay; autophagy substrate assay Autophagy Medium 29995557
2018 USP14 directly interacts with and stabilizes FASN (fatty acid synthase) by deubiquitination; USP14 overexpression promotes liver triglyceride accumulation in mice, while genetic ablation or pharmacological inhibition of USP14 ameliorates hepatosteatosis, hyperglycemia and insulin resistance in obese mice. Proteome, ubiquitinome and interactome analysis; Co-immunoprecipitation; in vivo mouse models (overexpression and knockout); IU1 pharmacological inhibition Nature communications High 30425250
2018 TRIM11 binds both the proteasome and USP14, precluding their association, thereby relieving USP14-mediated noncatalytic inhibition of the proteasome and increasing overall proteasome activity and protein degradation. Co-immunoprecipitation; in vitro proteasome activity assays; knockdown/overexpression experiments Nature communications Medium 29581427
2018 USP14 promotes K48-linked ubiquitination and proteasome-mediated degradation of IκBα by removing its ubiquitin chain, thereby promoting NF-κB activation. USP14 was found to associate with RelA, which acts as a linker between USP14 and IκBα. LPS treatment induces serine phosphorylation of USP14. Co-immunoprecipitation; ubiquitination assay; cycloheximide chase; Western blot; cytokine ELISA The Journal of biological chemistry Medium 23615914
2018 USP14 promotes mitophagy independently of PINK1 and Parkin by triggering mitochondrial fragmentation and membrane rupture that exposes the LC3 receptor Prohibitin 2; genetic and pharmacological inhibition of USP14 corrects mitochondrial dysfunction and locomotion defects in PINK1/Parkin mutant Drosophila. Genetic and pharmacological (IU1) USP14 inhibition in cell lines and Drosophila PD model; LC3/Prohibitin 2 localization; mitochondrial morphology assays; behavior tests EMBO molecular medicine Medium 30249595
2018 USP14 directly interacts with CXCR4 or its C-terminus in a CXCL12-stimulated, time-dependent manner; USP14 catalyzes CXCR4 deubiquitination. Knockdown of USP14 blocks deubiquitination and CXCR4 degradation, while overexpression promotes deubiquitination. Both overexpression and knockdown of USP14 block CXCL12-mediated chemotaxis, indicating that a ubiquitination-deubiquitination cycle on CXCR4 is required for chemotaxis. ERK activation is independent of CXCR4 ubiquitination status. Co-immunoprecipitation; co-localization by immunofluorescence; RNAi knockdown; ubiquitination assays; chemotaxis assays; use of ubiquitination-deficient CXCR4 mutant The Journal of biological chemistry Medium 19106094
2019 USP14 stabilizes CBP (CREB-binding protein) via deubiquitination, thereby enhancing glucagon action and hepatic gluconeogenesis. ER stress upregulates USP14 expression; liver-specific USP14 knockdown abrogates ER stress-induced effects on glucose metabolism and improves hyperglycemia in obese mice. In vivo hepatic USP14 overexpression and knockdown; ubiquitination assays; Co-immunoprecipitation; glucose tolerance tests in obese mice Proceedings of the National Academy of Sciences of the United States of America Medium 31594848
2019 USP14 interacts with the chaperone HSC70 in neuroblastoma cells; proteasome inhibition enhances USP14-HSC70 binding and also promotes interaction with XBP1u and IRE1α (UPR components). Inhibition of HSC70 downregulates USP14, and proteasome inhibition or W58A-USP14 (proteasome-binding mutant) promotes USP14 interaction with GABARAP, increasing autophagosomes. MS-based interactomics; co-immunoprecipitation; pharmacological HSC70 inhibition; fluorescence microscopy of autophagosomes iScience Medium 31901637
2019 USP14 inhibition (via IU1 inhibitor or siRNA) impairs autophagic flux specifically at the autophagosome-lysosome fusion step, with UVRAG as a checkpoint. This indicates USP14 activity has opposing roles in the two major proteolytic pathways: its inhibition enhances proteasomal activity but simultaneously blocks autophagic flux. Autophagy flux assays (LC3 lipidation, p62 accumulation); lysosomal fusion assays; USP14 pharmacological inhibition and siRNA; UVRAG functional analysis Cell reports Medium 30021169
2020 USP14 is a deubiquitinase for Ku70; mass spectrometry identified USP14 interaction with Ku70 and other NHEJ proteins, and an in vitro assay confirmed USP14 directly deubiquitinates Ku70. AKT-mediated Ser432 phosphorylation of USP14 is required for its DSB recruitment (IRIF formation). USP14 negatively regulates NHEJ in autophagy- and PTEN-deficient cells. Mass spectrometry; co-immunoprecipitation; in vitro deubiquitination assay; NHEJ reporter assay; immunofluorescence IRIF formation Nucleic acids research Medium 31740976
2020 USP14 directly deubiquitinates K63-linked ubiquitin chains on RIG-I; USP14 knockdown enhances RIG-I-triggered type I IFN signaling and inhibits VSV replication, while overexpression attenuates IFN-β expression, identifying USP14 as a negative regulator of antiviral immunity. Co-immunoprecipitation; ubiquitination assay (K63-linkage specific); siRNA knockdown; viral replication assays; in vivo mouse experiments with IU1 European journal of immunology Medium 30466171
2022 High-resolution cryo-EM of human USP14 bound to the 26S proteasome in 13 distinct conformational states revealed: ubiquitin-dependent activation of USP14 allosterically reprograms the AAA-ATPase motor conformation and stimulates core particle gate opening; dynamic USP14-ATPase interactions decouple ATPase activity from RPN11 deubiquitination; USP14 introduces three regulatory checkpoints at ubiquitin recognition, substrate translocation initiation, and ubiquitin chain recycling steps. Time-resolved single-particle cryo-EM; conformational state classification of proteasome intermediates during degradation of polyubiquitylated proteins Nature High 35477760
2022 Cryo-EM structures of yeast proteasome bound to Ubp6 identified an ILR element within the BL1 loop that mediates Rpt1 interaction to activate Ubp6; mutations in the ILR element abrogate both Ubp6 activation and its noncatalytic proteasome inhibition, demonstrating these two functions are mechanistically linked via the same interface. Ubp6 and ubiquitin together drive the proteasome into a unique inhibited conformation. Single-particle cryo-EM; site-directed mutagenesis of Ubp6 and Rpt1; biochemical activity assays with mutants Nature communications High 35149681
2022 USP14 directly deubiquitinates IDO1 via its deubiquitinase activity, stabilizing the IDO1 protein; knockdown or inhibition of USP14 decreases IDO1 expression, reverses T-cell suppression, and increases responsiveness to anti-PD-1 therapy in a syngeneic mouse model. Co-immunoprecipitation; ubiquitination assay; knockdown and pharmacological inhibition of USP14; in vivo syngeneic mouse model (MC38) Nature communications Medium 36163134
2022 USP14 catalyzes K48-linked deubiquitination of TAZ, promoting TAZ stabilization; TAZ in turn facilitates transcription of USP14 by binding TEAD1/4 response elements in the USP14 promoter, creating a self-amplifying feedback loop. USP14 does not stabilize the TAZ paralog YAP. DUB library screening; Co-immunoprecipitation; ubiquitination assays (K48-linkage specific); ChIP/luciferase reporter assays; in vivo xenograft and liver metastasis models Cell death and differentiation Medium 35906484
2019 Usp14 controls ciliogenesis, cilia elongation, and Hedgehog (Hh) signal transduction in mammalian cells; pharmacological inhibition of Usp14 positively affects Hh signaling in a polycystic kidney disease model. Usp14 knockdown and pharmacological inhibition; cilia length measurements by immunofluorescence; Hh signaling reporter assays Human molecular genetics Medium 30388222
2017 USP14 interacts with and deubiquitinates vimentin, stabilizing it in gastric cancer cells. Co-immunoprecipitation; ubiquitination assay Oncotarget Low 27448976
2017 USP14 associates with and stabilizes Aurora kinase B by preventing its FBXW7-mediated ubiquitination and degradation; USP14 overexpression inhibits chemotherapy drug-induced apoptosis in leukemia cells. Co-immunoprecipitation; cycloheximide chase; deubiquitination assay; flow cytometry apoptosis assays Cellular physiology and biochemistry Low 28662510
2019 USP14 interacts with and deubiquitinates CyclinB1, preventing its APC/C-mediated degradation; USP14 knockdown increases CyclinB1 ubiquitination and arrests cells at G2/M phase in breast cancer cells. Co-immunoprecipitation; ubiquitination assay; flow cytometry cell cycle analysis; USP14 siRNA knockdown Pathology, research and practice Low 31474315
2022 USP14 interacts with and stabilizes CDK1 by deubiquitinating K48-linked ubiquitin chains; USP14 inhibition causes G2/M cell cycle arrest in breast cancer cells. Co-immunoprecipitation; ubiquitination assay (K48-linkage specific); flow cytometry; siRNA knockdown Acta biochimica et biophysica Sinica Low 36604147
2023 USP14 interacts with and stabilizes JNK by deubiquitination; USP14 ablation reduces JNK protein levels and MAPK/JNK pathway activation, suppressing colorectal tumorigenesis in vitro and in vivo. TNF-α induces USP14 expression, forming a positive feedback loop with JNK. Co-immunoprecipitation; ubiquitination assay; RNA-seq and luciferase reporter pathway analysis; in vivo colorectal tumor models Cell death & disease Low 36693850
2023 USP14 deubiquitinates IκBα (removing K48-linked ubiquitin) and binds both IκBα and RELA, reducing IκBα stability and thereby promoting NF-κB activation and IκBα degradation in HNSCC cells. Co-immunoprecipitation; ubiquitination assay (K48-linkage specific); NF-κB reporter assay; nuclear fractionation; pharmacological and genetic USP14 inhibition Cell death and differentiation Medium 37055579
2021 USP14 deubiquitinates and stabilizes NLRP3; USP14 knockdown induces NLRP3 ubiquitination and inhibits pyroptosis of annulus fibrosus cells, while USP14 overexpression promotes pyroptosis through NLRP3/Caspase-1/IL-1β signaling. Co-immunoprecipitation; ubiquitination assay; flow cytometry (pyroptosis); ELISA (IL-1β, IL-18); gain/loss-of-function experiments Acta biochimica et biophysica Sinica Low 36514221
2022 USP14 deubiquitinates and stabilizes SIRT1 in macrophages, promoting fatty acid oxidation and M2/immunosuppressive macrophage polarization in the tumor microenvironment. Co-immunoprecipitation; ubiquitination assay; FAO (fatty acid oxidation) assays; OCR measurement; IU1 inhibition in tumor-bearing mice Biochemical and biophysical research communications Low 36701891
2023 USP14 deubiquitinates HSP90AA1 (reducing K48-linked ubiquitination), stabilizing it; elevated HSP90AA1 in turn promotes CYP2E1 protein accumulation, driving NAFLD progression through oxidative stress and mitochondrial dysfunction. Co-immunoprecipitation; ubiquitination assay; in vivo mouse models; hepatocyte-specific USP14 overexpression and knockdown Cell death & disease Medium 37633951
2024 IFNα increases TRIM14 transcription, which recruits USP14 to remove K63-linked ubiquitin chains from PD-L1, thereby preventing p62-mediated recognition and autophagic degradation of PD-L1, leading to immune evasion. Co-immunoprecipitation; ubiquitination assay (K63-linkage specific); autophagy flux assays; in vivo tumor models with IU1 + IFNα + anti-CTLA4 combination Cancer research Medium 38424493
2025 USP14 stabilizes the m6A demethylase ALKBH5 by preventing its K48-linked ubiquitination and degradation (mediated by HECW2); MST4 kinase phosphorylates ALKBH5 at Ser64/69, increasing its interaction with USP14 and promoting deubiquitylation. ALKBH5 in turn interacts with the USP14 transcript in a YTHDF2-dependent manner to sustain USP14 overexpression, forming a positive feedback loop that promotes glioblastoma stem cell radioresistance. Mass spectrometry; co-immunoprecipitation; ubiquitination assay; phosphorylation mapping; m6A-seq; transcriptome analysis; in vivo xenograft models Theranostics Medium 39990235
2021 USP14 directly binds ubiquitin chains on viral VP16 protein through its UBL domain; USP14 inactivation triggers EIF2AK3/PERK- and ERN1/IRE1-mediated ER stress, which drives K63-linked ubiquitination of VP16 and its degradation via SQSTM1/p62-mediated selective autophagy, inhibiting alphaherpesvirus replication. Co-immunoprecipitation; ubiquitination assay; ER stress pathway analysis; USP14 null cell rescue; CRISPR knockout; in vivo mouse model Autophagy Medium 34822318
2022 USP14 interacts with, deubiquitinates, and stabilizes MFG-E8 in human bronchial epithelial cells, inhibiting its proteasomal degradation; cigarette smoke reduces USP14 expression, decreasing MFG-E8 abundance and antiferroptotic protection. Co-immunoprecipitation; ubiquitination assay; siRNA knockdown; Western blot Cell death & disease Low 36596780
2020 USP14 directly binds TRAF6 and blocks the USP14-TRAF6 interaction; USP14 inhibition (via compound S5) promotes K63-linked ubiquitination of Beclin1, disrupts Beclin1-Bcl2 interaction, and promotes autophagosome accumulation in M1 macrophages, blocking M1 polarization and alleviating sepsis in CLP mice. Molecular docking; Co-immunoprecipitation; ubiquitination assay; autophagy flux assays; in vivo CLP mouse model Cell death & disease Low 32820146
2024 ALDH2 reduces the interaction between USP14 and cGAS, promoting K48-linked polyubiquitination and degradation of cGAS at lysine 282 in macrophages; USP14 knockdown in bone marrow cells alleviated proinflammatory responses and protected against atherosclerosis. Co-immunoprecipitation; ubiquitination assay (K48-linkage, site-specific); bone marrow transplantation; in vivo atherosclerosis model Redox biology Medium 39178733
2022 USP14 deubiquitinates and stabilizes NLRC5; USP14 overexpression in endothelial cells restrains ox-LDL-stimulated NF-κB activation by protecting NLRC5 from degradation, and USP14 adenoviral overexpression in ApoE−/− mice reduces atherosclerotic lesions. Co-immunoprecipitation; ubiquitination assay; in vivo ApoE−/− mouse model with adenoviral USP14 overexpression; NF-κB reporter assay Biochimica et biophysica acta. Molecular and cell biology of lipids Low 36372300
2023 GSTM3 stabilizes USP14, which in turn inhibits ubiquitination and degradation of FASN, leading to ferroptosis promotion in NPC under ionizing radiation. Co-immunoprecipitation; mass spectrometry; immunofluorescence; ubiquitination assay British journal of cancer Low 38228715
2020 Inactive USP14 C114A mutant (requiring intact proteasome-binding domain) causes accumulation of specific ubiquitinated proteins at the proteasome, including β-catenin, which does not accumulate with inactive UCHL5 C88A, demonstrating substrate selectivity between the two proteasome-associated DUBs. USP14 also regulates deubiquitination of proteasomal subunits PSMC1 and PSMD4. USP14 C114A inactive mutant expression; ubiquitin immunoprecipitation; mass spectrometry; immunoprecipitation/immunoblotting validation PloS one Medium 31703099
2014 Yeast Ubp6 processes Lys11 and Lys63 polyubiquitin chains with increasing efficiency as chain length increases, and shows endo-chain cleavage preference for K48-linked chains (in contrast to Rpn11's random cleavage). Proteasomes deconjugate ubiquitin substrates ~100-fold more efficiently than constituent DUBs alone; incorporation into proteasomes significantly enhances Rpn11 catalytic efficiency. In vitro deubiquitination assays with defined homogeneous and heterogeneous polyubiquitin conjugates; fluorescently labeled Ub chain substrates; kinetic analysis The Journal of biological chemistry High 25389291

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. The EMBO journal 360 16211010
2006 Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell 298 17018280
2013 A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood 274 24319254
2002 Synaptic defects in ataxia mice result from a mutation in Usp14, encoding a ubiquitin-specific protease. Nature genetics 227 12368914
2016 USP14 deubiquitinates proteasome-bound substrates that are ubiquitinated at multiple sites. Nature 177 27074503
2022 USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer. Nature communications 157 36163134
2013 MicroRNA-124 protects against focal cerebral ischemia via mechanisms involving Usp14-dependent REST degradation. Acta neuropathologica 136 23754622
2017 An inhibitor of the proteasomal deubiquitinating enzyme USP14 induces tau elimination in cultured neurons. The Journal of biological chemistry 126 28972160
2018 Proteome-wide analysis of USP14 substrates revealed its role in hepatosteatosis via stabilization of FASN. Nature communications 123 30425250
2003 Complementary roles for Rpn11 and Ubp6 in deubiquitination and proteolysis by the proteasome. The Journal of biological chemistry 121 14581483
2005 Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice. Journal of neurochemistry 110 16190881
2013 Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling. Oncogenesis 107 23958854
2009 The proteasome-associated deubiquitinating enzyme Usp14 is essential for the maintenance of synaptic ubiquitin levels and the development of neuromuscular junctions. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 19726649
2018 Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination. Oncogene 104 29353883
2022 USP14: Structure, Function, and Target Inhibition. Frontiers in pharmacology 100 35069211
2013 Over-expression of deubiquitinating enzyme USP14 in lung adenocarcinoma promotes proliferation through the accumulation of β-catenin. International journal of molecular sciences 98 23702845
2015 Structural characterization of the interaction of Ubp6 with the 26S proteasome. Proceedings of the National Academy of Sciences of the United States of America 95 26130806
2003 Pleiotropic effects of Ubp6 loss on drug sensitivities and yeast prion are due to depletion of the free ubiquitin pool. The Journal of biological chemistry 95 14559899
2018 USP14 inhibition corrects an in vivo model of impaired mitophagy. EMBO molecular medicine 92 30249595
2008 Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK ativation. The Journal of biological chemistry 91 19106094
2019 Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide. Journal of experimental & clinical cancer research : CR 80 31126320
2017 The deubiquitinating enzyme Usp14 allosterically inhibits multiple proteasomal activities and ubiquitin-independent proteolysis. The Journal of biological chemistry 75 28416611
2022 USP14-regulated allostery of the human proteasome by time-resolved cryo-EM. Nature 72 35477760
2018 USP14 regulates DNA damage repair by targeting RNF168-dependent ubiquitination. Autophagy 71 29995557
2018 Dual Function of USP14 Deubiquitinase in Cellular Proteasomal Activity and Autophagic Flux. Cell reports 71 30021169
2008 Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity. Molecular and cellular neurosciences 71 18771733
2013 Overexpression of USP14 protease reduces I-κB protein levels and increases cytokine release in lung epithelial cells. The Journal of biological chemistry 67 23615914
2021 Inhibition of USP14 influences alphaherpesvirus proliferation by degrading viral VP16 protein via ER stress-triggered selective autophagy. Autophagy 65 34822318
2018 UBL domain of Usp14 and other proteins stimulates proteasome activities and protein degradation in cells. Proceedings of the National Academy of Sciences of the United States of America 64 30487212
2017 USP14 inhibitor attenuates cerebral ischemia/reperfusion-induced neuronal injury in mice. Journal of neurochemistry 64 28029679
2014 MiR-4782-3p inhibited non-small cell lung cancer growth via USP14. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 64 24556800
2017 Ubiquitinated proteins promote the association of proteasomes with the deubiquitinating enzyme Usp14 and the ubiquitin ligase Ube3c. Proceedings of the National Academy of Sciences of the United States of America 63 28396413
2017 USP14 de-ubiquitinates vimentin and miR-320a modulates USP14 and vimentin to contribute to malignancy in gastric cancer cells. Oncotarget 62 27448976
2018 TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14. Nature communications 60 29581427
2014 Ubiquitin-specific protease 14 (USP14) regulates cellular proliferation and apoptosis in epithelial ovarian cancer. Medical oncology (Northwood, London, England) 60 25429837
2015 Targeted inhibition of the deubiquitinating enzymes, USP14 and UCHL5, induces proteotoxic stress and apoptosis in Waldenström macroglobulinaemia tumour cells. British journal of haematology 57 25691154
2015 Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity. Scientific reports 57 26041011
2011 The catalytic activity of Ubp6 enhances maturation of the proteasomal regulatory particle. Molecular cell 56 21658604
2015 USP14 activation promotes tumor progression in hepatocellular carcinoma. Oncology reports 54 26397990
2016 Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells. Blood cancer journal 53 27813535
2021 Suppressing long noncoding RNA OGRU ameliorates diabetic retinopathy by inhibition of oxidative stress and inflammation via miR-320/USP14 axis. Free radical biology & medicine 51 33762162
2021 USP14 maintains HIF1-α stabilization via its deubiquitination activity in hepatocellular carcinoma. Cell death & disease 50 34420039
2019 Sustained ER stress promotes hyperglycemia by increasing glucagon action through the deubiquitinating enzyme USP14. Proceedings of the National Academy of Sciences of the United States of America 48 31594848
2020 Inhibition of USP14 suppresses the formation of foam cell by promoting CD36 degradation. Journal of cellular and molecular medicine 45 31970862
2019 USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro. International journal of molecular sciences 44 31653087
2022 A self-amplifying USP14-TAZ loop drives the progression and liver metastasis of pancreatic ductal adenocarcinoma. Cell death and differentiation 43 35906484
2020 USP14 is a deubiquitinase for Ku70 and critical determinant of non-homologous end joining repair in autophagy and PTEN-deficient cells. Nucleic acids research 43 31740976
2018 Targeting the Proteasome-Associated Deubiquitinating Enzyme USP14 Impairs Melanoma Cell Survival and Overcomes Resistance to MAPK-Targeting Therapies. Molecular cancer therapeutics 43 29703842
2015 Downregulation of ubiquitin-specific protease 14 (USP14) inhibits breast cancer cell proliferation and metastasis, but promotes apoptosis. Journal of molecular histology 41 26712154
2024 GSTM3 enhances radiosensitivity of nasopharyngeal carcinoma by promoting radiation-induced ferroptosis through USP14/FASN axis and GPX4. British journal of cancer 40 38228715
2023 USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1. Cell death & disease 40 37633951
2016 USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment. Oncotarget 40 27121063
2018 USP14 promotes K63-linked RIG-I deubiquitination and suppresses antiviral immune responses. European journal of immunology 39 30466171
2018 USP14-mediated IκBα degradation exacerbates NF-κB activation and IL-1β-stimulated chondrocyte dedifferentiation. Life sciences 39 30550885
2020 Lidocaine inhibits the proliferation and invasion of hepatocellular carcinoma by downregulating USP14 induced PI3K/Akt pathway. Pathology, research and practice 38 32471606
2013 A catalytic independent function of the deubiquitinating enzyme USP14 regulates hippocampal synaptic short-term plasticity and vesicle number. The Journal of physiology 38 24218545
2016 Function of Deubiquitinating Enzyme USP14 as Oncogene in Different Types of Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 37 26938858
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
2023 MFG-E8 stabilized by deubiquitinase USP14 suppresses cigarette smoke-induced ferroptosis in bronchial epithelial cells. Cell death & disease 36 36596780
2020 Typically inhibiting USP14 promotes autophagy in M1-like macrophages and alleviates CLP-induced sepsis. Cell death & disease 36 32820146
2009 USP14 inhibits ER-associated degradation via interaction with IRE1alpha. Biochemical and biophysical research communications 35 19135427
2023 USP14 promotes colorectal cancer progression by targeting JNK for stabilization. Cell death & disease 34 36693850
2023 Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC). Cell death and differentiation 34 37055579
2020 USP14 Regulates DNA Damage Response and Is a Target for Radiosensitization in Non-Small Cell Lung Cancer. International journal of molecular sciences 33 32887472
2023 USP14 inhibition promotes recovery by protecting BBB integrity and attenuating neuroinflammation in MCAO mice. CNS neuroscience & therapeutics 32 37269080
2019 CyclinB1 deubiquitination by USP14 regulates cell cycle progression in breast cancer. Pathology, research and practice 32 31474315
1997 Purification and characterization of UBP6, a new ubiquitin-specific protease in Saccharomyces cerevisiae. Archives of biochemistry and biophysics 29 9344467
2019 The deubiquitinating enzyme Usp14 controls ciliogenesis and Hedgehog signaling. Human molecular genetics 28 30388222
2017 The Deubiquitinating Enzyme USP14 Regulates Leukemic Chemotherapy Drugs-Induced Cell Apoptosis by Suppressing Ubiquitination of Aurora Kinase B. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 28662510
2012 Usp14 deficiency increases tau phosphorylation without altering tau degradation or causing tau-dependent deficits. PloS one 28 23144711
2024 Targeting the TRIM14/USP14 Axis Enhances Immunotherapy Efficacy by Inducing Autophagic Degradation of PD-L1. Cancer research 27 38924473
2022 USP14-mediated deubiquitination of SIRT1 in macrophage promotes fatty acid oxidation amplification and M2 phenotype polarization. Biochemical and biophysical research communications 27 36701891
2022 Allosteric control of Ubp6 and the proteasome via a bidirectional switch. Nature communications 26 35149681
2024 CircPDE5A-encoded novel regulator of the PI3K/AKT pathway inhibits esophageal squamous cell carcinoma progression by promoting USP14-mediated de-ubiquitination of PIK3IP1. Journal of experimental & clinical cancer research : CR 25 38658954
2022 Inhibition of USP14 suppresses ferroptosis and inflammation in LPS-induced goat mammary epithelial cells through ubiquitylating the IL-6 protein. Hereditas 25 35549778
2016 Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases? F1000Research 25 26998235
2024 USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis. Molecular medicine (Cambridge, Mass.) 24 38424494
2024 ALDH2 deficiency augments atherosclerosis through the USP14-cGAS-dependent polarization of proinflammatory macrophages. Redox biology 24 39178733
2023 Ceramide Synthase 1 Inhibits Brain Metastasis of Non-Small Cell Lung Cancer by Interacting with USP14 and Downregulating the PI3K/AKT/mTOR Signaling Pathway. Cancers 24 37046655
2019 Dynamic Interaction of USP14 with the Chaperone HSC70 Mediates Crosstalk between the Proteasome, ER Signaling, and Autophagy. iScience 23 31901637
2016 Inhibition of deubiquitinating activity of USP14 decreases tyrosine hydroxylase phosphorylated at Ser19 in PC12D cells. Biochemical and biophysical research communications 23 26969276
2022 USP14 promotes pyroptosis of human annulus fibrosus cells derived from patients with intervertebral disc degeneration through deubiquitination of NLRP3. Acta biochimica et biophysica Sinica 22 36514221
2020 Inhibition of USP14 induces ER stress-mediated autophagy without apoptosis in lung cancer cell line A549. Cell stress & chaperones 22 32632734
2022 USP14 regulates cell cycle progression through deubiquitinating CDK1 in breast cancer. Acta biochimica et biophysica Sinica 21 36604147
2020 USP14 negatively regulates RIG-I-mediated IL-6 and TNF-α production by inhibiting NF-κB activation. Molecular immunology 21 33360745
2022 Inhibition of USP14 Suppresses ROS-dependent Ferroptosis and Alleviates Renal Ischemia/Reperfusion Injury. Cell biochemistry and biophysics 19 36255562
2022 USP14-mediated NLRC5 upregulation inhibits endothelial cell activation and inflammation in atherosclerosis. Biochimica et biophysica acta. Molecular and cell biology of lipids 19 36372300
2025 USP14 modulates stem-like properties, tumorigenicity, and radiotherapy resistance in glioblastoma stem cells through stabilization of MST4-phosphorylated ALKBH5. Theranostics 18 39990235
2023 SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1. International journal of biological sciences 18 37496999
2023 Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells. Acta pharmacologica Sinica 18 37528233
2020 USP14 as a Therapeutic Target Against Neurodegeneration: A Rat Brain Perspective. Frontiers in cell and developmental biology 18 32850842
2020 Discovery of new promising USP14 inhibitors: computational evaluation of the thumb-palm pocket. Journal of biomolecular structure & dynamics 18 33170088
2023 Yap1-Usp14 Axis Inhibits Neuronal Mitophagy During Neonatal Hypoxia-Ischemia Encephalopathy by Regulation of Beclin-1 Ubiquitination in Mouse. Molecular neurobiology 17 37062801
2021 Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK/NF-κB signaling. Immunity, inflammation and disease 17 34089575
2019 Inactive USP14 and inactive UCHL5 cause accumulation of distinct ubiquitinated proteins in mammalian cells. PloS one 17 31703099
2016 Knockdown of Ubiquitin-Specific Protease 14 (USP14) Inhibits the Proliferation and Tumorigenesis in Esophageal Squamous Cell Carcinoma Cells. Oncology research 17 27629392
2024 miR-26a-5p Attenuates Oxidative Stress and Inflammation in Diabetic Retinopathy through the USP14/NF-κB Signaling Pathway. Journal of ophthalmology 16 38282961
2013 Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14). PloS one 16 24358326
2007 [Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 16 17553343
2022 Inhibition of USP14 enhances anti-tumor effect in vemurafenib-resistant melanoma by regulation of Skp2. Cell biology and toxicology 15 35648318

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