Affinage

USP47

Ubiquitin carboxyl-terminal hydrolase 47 · UniProt Q96K76

Length
1375 aa
Mass
157.3 kDa
Annotated
2026-06-11
49 papers in source corpus 34 papers cited in narrative 34 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

USP47 is a cysteine deubiquitylase that stabilizes a broad array of substrate proteins by removing ubiquitin chains and antagonizing their proteasomal degradation, positioning it as a central regulator across DNA repair, Wnt and Hedgehog signaling, immunity, and cell proliferation (PMID:21362556, PMID:26169834, PMID:36749823). Crystal structures of its catalytic domain show that its catalytic triad is misaligned in the free state and becomes competent upon ubiquitin binding, and the full-length enzyme is more active than the isolated catalytic domain (PMID:37740002). In genome maintenance, USP47 is the major deubiquitylase for DNA polymerase β, stabilizing the cytoplasmic pool that supplies nuclear base excision repair, and it likewise stabilizes FEN1 and the spliceosomal factor IK to support DNA damage repair (PMID:21362556, PMID:42112089, PMID:32377397). USP47 functions in concert with the SCF(β-TrCP) ligase machinery: it binds β-TrCP1/2 directly and these interactions feed into Wnt/β-catenin and Hedgehog outputs, including direct deubiquitylation of β-catenin and of the Groucho/TLE co-repressor to promote Wnt-TCF target gene expression (PMID:19966869, PMID:26169834, PMID:31341163, PMID:36749823). In the cytoplasm and at the cell cortex it stabilizes katanin-p60 to promote axonal growth and is recruited by the motor KIFC3 to deubiquitylate E-cadherin at adherens junctions (PMID:23904609, PMID:25253721). USP47 also tunes immune and inflammatory signaling — it is required for NLRP3 inflammasome assembly, removes K63-linked chains from TRAF3/TRAF6 to attenuate type I interferon production, and in regulatory T cells stabilizes YTHDF1 to control m6A-dependent c-Myc translation (PMID:30206189, PMID:37001379, PMID:37788092). A recurring theme in cancer is USP47-mediated stabilization of oncogenic and metabolic regulators including c-Myc, BACH1, YBX1, SATB1, and PD-L1, making it a recurrent therapeutic target whose pharmacological inhibition lowers these substrates and sensitizes tumors (PMID:40180254, PMID:35141006, PMID:33397955, PMID:30742943, PMID:40494207).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2009 Medium

    Established USP47 as a physical partner of the SCF(β-TrCP) ligase, defining its connection to the ubiquitin–proteasome degradation machinery and to cell-cycle/survival control.

    Evidence Co-IP with point mutagenesis of β-TrCP WD-repeats and siRNA knockdown with survival readout

    PMID:19966869

    Open questions at the time
    • Direct deubiquitylation of a substrate not yet demonstrated
    • How USP47 modulates β-TrCP function mechanistically unclear
  2. 2011 High

    Identified the first bona fide USP47 substrate, DNA polymerase β, linking the enzyme to base excision repair fidelity.

    Evidence siRNA knockdown, ubiquitylation assays, and DNA strand-break/BER functional assays

    PMID:21362556

    Open questions at the time
    • Site of deubiquitylation on Pol β not mapped
    • In vitro reconstitution with purified components not shown
  3. 2013 High

    Showed USP47 directly antagonizes a specific E3 ligase (CHIP) to stabilize katanin-p60, demonstrating a deubiquitylase–ligase counterbalance with a developmental phenotype.

    Evidence Reciprocal Co-IP, ubiquitination assays, and axonal-growth assays in cultured neurons with bFGF stimulation

    PMID:23904609

    Open questions at the time
    • Chain type removed not defined
    • Upstream regulation of USP47 by bFGF not resolved
  4. 2014 High

    Revealed spatial control of USP47 activity, with motor KIFC3 recruiting it to adherens junctions to protect E-cadherin from Hakai-mediated cleavage.

    Evidence Co-IP, siRNA knockdown, E-cadherin ubiquitination assay, and immunofluorescence

    PMID:25253721

    Open questions at the time
    • Direct vs indirect deubiquitylation of E-cadherin not distinguished
    • Structural basis of KIFC3 binding unknown
  5. 2015 High

    Defined USP47 as a Wnt pathway component that deubiquitylates β-catenin, validated across species, and uncovered its reciprocal regulation by and auto-deubiquitylation within the β-TrCP system.

    Evidence RNAi screen, Co-IP, ubiquitination assays, and Drosophila in vivo genetics

    PMID:26169834

    Open questions at the time
    • Stoichiometry between USP47 self-regulation and substrate turnover unclear
  6. 2016 High

    Positioned USP47 as a counter-force to the N-end rule (UBR4/POE) degradation module to maintain MAPK levels and RAS-MAPK output.

    Evidence RNAi-based genetic interaction/epistasis screen in Drosophila with MAPK level measurements

    PMID:27552662

    Open questions at the time
    • Direct biochemical deubiquitylation of MAPK not shown
    • Conservation in mammalian cells not tested here
  7. 2018 High

    Extended USP47 function into innate immunity by showing it is required for NLRP3 inflammasome assembly and ASC speck formation.

    Evidence Chemical inhibition, CRISPR/Cas9 knockdown, ASC oligomerization and NLRP3 ubiquitination assays, cytokine measurement

    PMID:30206189

    Open questions at the time
    • Inhibitors target both USP7 and USP47, limiting USP47-specific attribution
    • Direct NLRP3 substrate relationship not isolated
  8. 2019 High

    Connected USP47 to Hedgehog signaling through an ERAP1–USP47–β-TrCP ternary complex that controls Gli activity, and to SATB1 stabilization in cancer.

    Evidence Co-IP, pulldown, and in vitro/in vivo tumor models; separate SATB1 Co-IP/ubiquitination work

    PMID:30742943 PMID:31341163

    Open questions at the time
    • Whether USP47 catalytic activity is required for the ERAP1 effect not separated from scaffolding
  9. 2020 Medium

    Linked USP47 to ribosomal-stress p53 signaling and to splicing fidelity, stabilizing RPS2 and the spliceosomal factor IK that ensures correct ATM pre-mRNA splicing.

    Evidence Co-IP, ubiquitination assays, splicing assays, and xenograft models

    PMID:32370049 PMID:32377397

    Open questions at the time
    • Single-lab evidence for each substrate
    • Catalytic dependence of RPS2 effect not formally tested
  10. 2022 High

    Defined the catalytic mechanism: ubiquitin binding aligns the misaligned catalytic triad and full-length enzyme exceeds the isolated catalytic domain in activity; in parallel, multiple oncogenic/immune substrates (BACH1, RPL11/p53, TRAF3/6, EZH2) were established.

    Evidence X-ray crystallography with deubiquitinase assays; plus Co-IP/ubiquitination assays and catalytically inactive mutant controls across substrate studies

    PMID:35034955 PMID:35141006 PMID:35205710 PMID:37001379 PMID:37740002

    Open questions at the time
    • No full-length structure to explain higher activity
    • Substrate-specific recognition determinants in BL loops not mapped to individual substrates
  11. 2023 High

    Showed USP47 controls Treg metabolism via YTHDF1-dependent m6A c-Myc translation and deubiquitylates the Groucho/TLE co-repressor to drive Wnt target gene expression, broadening its regulatory reach into translation and transcriptional co-repression.

    Evidence Treg-specific knockout mouse, m6A translation/metabolic assays; genome-scale RNAi screen with in vitro ubiquitylation inhibition across three organisms

    PMID:36749823 PMID:37788092

    Open questions at the time
    • Direct YTHDF1 deubiquitylation site not mapped
    • Relative contribution of β-catenin vs TLE deubiquitylation to Wnt output unresolved
  12. 2025 Medium

    Consolidated USP47 as a cancer therapeutic target, stabilizing c-Myc and PD-L1, with inhibition synergizing with KRAS-G12C inhibition and anti-PD-1 therapy.

    Evidence Co-IP, ubiquitination assays, T cell killing assays, and in vivo xenograft/HCC models with small-molecule inhibitors

    PMID:40180254 PMID:40494207

    Open questions at the time
    • Single-lab evidence per substrate
    • Inhibitor selectivity over USP7 not fully resolved in some studies
  13. 2026 Medium

    Expanded the substrate landscape into tissue-protective and pathological roles, stabilizing SIRT1, HDAC2, ASK1, PRMT5, NNT and GluR1 across liver, cardiac, muscle, skin and neuronal contexts.

    Evidence Co-IP, site-specific (ASK1 K805) and catalytic-mutant ubiquitination assays, ChIP-qPCR, electrophysiology, and in vivo disease models

    PMID:37924851 PMID:39436323 PMID:40716012 PMID:41529803 PMID:41903125 PMID:41930505

    Open questions at the time
    • Each substrate rests on single-lab evidence
    • Whether one cell type uses one dominant substrate axis is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP47 achieves substrate selectivity among its many reported targets and how its activity is spatially and temporally regulated remain open.
  • No substrate-recognition code linking BL loops to specific substrates
  • Regulation of USP47 catalytic activation in vivo undefined
  • Most substrate claims are single-lab

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 1 GO:0005730 nucleolus 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3
Partners
ASK1BTRCERAP1FBXW11KIFC3PRMT5TLE3XIAP

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 USP47 is the major deubiquitylating enzyme for DNA polymerase β (Pol β), stabilizing newly synthesized cytoplasmic Pol β that is used as a source for nuclear Pol β in DNA base excision repair (BER). Knockdown of USP47 increases ubiquitylated Pol β, decreases Pol β levels, and causes BER deficiency with accumulation of DNA strand breaks. siRNA knockdown, ubiquitylation assays, DNA damage assays, cell viability assays Molecular cell High 21362556
2009 USP47 physically interacts with SCF(β-TrCP) E3 ubiquitin ligase via direct binding to both β-TrCP1 and β-TrCP2 WD-repeat regions (point mutations in WD-repeat abolished binding). Unlike canonical β-TrCP substrates, USP47 levels were not regulated by β-TrCP. Depletion of USP47 caused accumulation of Cdc25A and decreased cell survival. Co-immunoprecipitation, point mutagenesis, siRNA knockdown, cell survival assays Oncogene Medium 19966869
2012 USP47 (together with USP7) is a cysteine isopeptidase whose inhibition stabilizes p53 and decreases DNA polymerase β (Pol β) levels in cancer cells, leading to apoptosis. Selective dual small-molecule inhibitors of USP7 and USP47 were shown to inhibit USP7 in cells and induce elevated p53. Small molecule inhibition, cell-based p53/apoptosis assays, in vivo xenograft models ACS medicinal chemistry letters Medium 24900381
2013 USP47 deubiquitinates and stabilizes katanin-p60 (a microtubule-severing enzyme), antagonizing CHIP (an E3 ubiquitin ligase that promotes katanin-p60 degradation). USP47 overexpression promoted axonal growth in rat hippocampal neurons, while CHIP overexpression inhibited it. bFGF treatment increased USP47 and katanin-p60 levels and decreased ubiquitinated katanin-p60. Co-immunoprecipitation, ubiquitination assays, overexpression/knockdown in cultured neurons, bFGF treatment The Journal of neuroscience High 23904609
2014 Minus end-directed motor KIFC3 binds USP47 and recruits it to adherens junctions. Depletion of KIFC3 or USP47 promotes ubiquitination and cleavage of E-cadherin at a juxtamembrane region (producing a 90-kDa fragment), dependent on the E3 ligase Hakai, leading to E-cadherin internalization. Proteasome inhibitors blocked this cleavage. Co-immunoprecipitation, siRNA knockdown, E-cadherin ubiquitination assay, proteasome inhibitor treatment, immunofluorescence Molecular biology of the cell High 25253721
2015 USP47 (and its Drosophila ortholog UBP64E) deubiquitinates β-catenin, preventing its ubiquitination and proteasomal degradation. RNAi inactivation of USP47 increased β-catenin ubiquitination, attenuated Wnt signaling, and repressed cancer cell growth. β-TrCP promotes USP47 ubiquitination via an atypical interaction motif, and USP47 also auto-deubiquitinates itself. In vivo, UBP64E is required for Armadillo stabilization and Wnt target gene expression in Drosophila wing. RNAi library screen, Co-immunoprecipitation, ubiquitination assays, Drosophila in vivo genetics Molecular and cellular biology High 26169834
2016 Drosophila USP47 acts post-translationally to stabilize MAPK by counteracting its proteasome-mediated degradation. Genetic interaction RNAi screening identified UBC6 (E2), POE/UBR4 (N-recognin E3 ligase), and UFD4 as enzymes opposing USP47. KCMF1 was identified as another component of the POE-associated degradation module. These results place USP47 as counteracting the N-end rule pathway to maintain MAPK levels and RAS-MAPK signaling output. RNAi-based genetic interaction screen, epistasis analysis in Drosophila, MAPK level measurements PLoS biology High 27552662
2018 Chemical inhibition of USP7 and USP47 blocks NLRP3 inflammasome formation in macrophages, independently of transcription, by preventing ASC oligomerisation and speck formation. The ubiquitination status of NLRP3 is altered by inhibition of USP7/USP47. USP7 and USP47 activity increases in response to inflammasome activators. CRISPR/Cas9 knockdown of both USP7 and USP47 reduces inflammasome activation and IL-1β/IL-18 release. Chemical inhibition, CRISPR/Cas9 knockdown, ASC oligomerization assay, NLRP3 ubiquitination assay, cytokine measurement EMBO reports High 30206189
2018 USP47 promotes β-TrCP stability and phosphorylation of RelA (NF-κB subunit) in gastric cancer cells. USP47 knockdown reduced cell viability and increased sensitivity to etoposide and camptothecin. Immunoblot, siRNA knockdown, MTT assay, Annexin V staining, PARP/caspase cleavage Biomedicines Low 29786670
2019 ERAP1 binds USP47, displaces the USP47-associated β-TrCP (substrate-receptor of SCFβ-TrCP ubiquitin ligase), and promotes β-TrCP degradation. This results in modulation of Gli transcription factors (effectors of Hedgehog signaling) and enhancement of Hh pathway activity. Co-immunoprecipitation, pulldown, genetic and pharmacological inhibition in vitro and in vivo tumor models Nature communications High 31341163
2019 USP47 interacts with SATB1 and mediates its deubiquitination and stabilization. SMURF2 is an E3 ubiquitin ligase that promotes SATB1 degradation. USP47 negatively regulates SMURF2, and USP47 depletion sensitizes colon cancer cells to 5-FU-induced apoptosis. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, mouse xenograft model Cancer letters Medium 30742943
2020 USP47 interacts with and deubiquitinates IK (a spliceosomal component), preventing its proteolytic degradation via the 26S proteasome. USP47-mediated stabilization of IK is required for proper splicing of ATM pre-mRNA (particularly intron 1), and IK deficiency impairs DNA damage repair. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, pre-mRNA splicing assay Cell death discovery Medium 32377397
2020 USP47 deubiquitinates ribosomal protein S2 (RPS2) that has been ubiquitinated by MDM2. Under normal conditions, USP47 inhibits the interaction between RPS2 and MDM2, alleviating RPS2-mediated MDM2 suppression and keeping p53 levels low. Under ribosomal stress, USP47 dissociation allows RPS2-MDM2 binding, suppresses MDM2, and induces p53 upregulation. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, xenograft mouse model Cancers Medium 32370049
2021 USP47 stabilizes Y-box binding protein 1 (YBX1), contributing to DNA damage repair in CML cells. USP47 knockdown or knockout significantly inhibited BCR-ABL and BCR-ABL(T315I)-induced CML in mice and reduced Lin-Sca1+c-Kit+ CML stem/progenitor cells. Mechanistic studies (YBX1 stabilization), in vitro knockdown, in vivo CML mouse models, flow cytometry for stem cell populations Nature communications Medium 33397955
2021 USP47 interacts with TCEA3 and mediates its deubiquitination, increasing intracellular TCEA3 levels. TCEA3 regulates pro-apoptotic Bax levels. USP47-TCEA3 axis modulates pyroptosis and apoptosis in response to doxorubicin in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, apoptosis/pyroptosis assays Frontiers in pharmacology Medium 34630087
2022 USP47 deubiquitinates and stabilizes BACH1 (BTB and CNC homology 1 transcription factor). USP47-stabilized BACH1 promotes the Warburg effect (glycolysis) in NSCLC by transcriptionally upregulating hexokinase 2 (Hk2) and GAPDH. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, in vitro/in vivo proliferation assays, glycolysis measurement American journal of cancer research Medium 35141006
2022 USP47 deubiquitinates RPL11, preventing its translocation from nucleolus to nucleoplasm. When USP47 is inhibited, RPL11 translocates to the nucleoplasm and interacts with MDM2, preventing MDM2-mediated proteasomal degradation of p53, thus inhibiting cell proliferation in a p53-dependent manner. The catalytically inactive USP47 form does not rescue this phenotype. miR-101-3p overexpression, USP47 overexpression with catalytically inactive mutant, Co-IP, immunofluorescence for RPL11 localization, cell proliferation assays Cancers Medium 35205710
2022 USP47 removes K63-linked polyubiquitin chains from TRAF3 and TRAF6, acting downstream of MAVS and upstream of TBK1 in the antiviral innate immune signaling pathway, thereby attenuating type I interferon production and IFNB1 transcription. Co-immunoprecipitation, ubiquitin chain-type specific assays, overexpression/knockdown, luciferase reporter assay, viral replication assay International immunopharmacology Medium 37001379
2022 USP47 inhibition leads to destabilization of mutant EZH2 protein through promotion of its ubiquitination. USP47 was identified as a novel regulator of mutant EZH2, and targeting USP47 leads to death of mutant EZH2-positive DLBCL cells in vitro and in vivo. Selectivity profiling, genetic knockdown, ubiquitination assay, in vitro and mouse model studies Leukemia Medium 35034955
2023 Crystal structures of the USP47 catalytic domain (free and ubiquitin-bound states) reveal misaligned catalytic triads that become aligned upon ubiquitin binding (similar to USP7), enabling catalysis. Full-length USP47 shows higher deubiquitinase activity than the catalytic domain alone. BL1, BL2, and BL3 loops differ from USP7 in composition and length, contributing to substrate selectivity. X-ray crystallography, in vitro deubiquitinase activity assays, domain truncation experiments Communications biology High 37740002
2023 USP47 prevents YTHDF1 ubiquitination to attenuate the association of YTHDF1 with translation initiation machinery, thereby decreasing m6A-based c-Myc translation efficiency in regulatory T cells. USP47 ablation in Tregs caused c-Myc protein accumulation, exacerbated hyperglycolysis, compromised Treg homeostasis, and boosted antitumor immune responses. Co-immunoprecipitation, ubiquitination assay, Treg-specific knockout mouse, m6A translation efficiency assays, metabolic assays The Journal of clinical investigation High 37788092
2023 USP47 deubiquitylates the transcriptional co-repressor Groucho/TLE, counteracting XIAP-mediated monoubiquitylation of TLE3. USP47 interacts with both TLE3 and XIAP but does not alter their amounts. USP47 inhibited XIAP-mediated ubiquitylation of TLE3 in vitro in a dose-dependent manner. This deubiquitylation is required for Wnt-β-catenin target gene expression in Drosophila, Xenopus, and human cells. Genome-scale RNAi screen in Drosophila, Co-immunoprecipitation, in vitro ubiquitylation assay, Xenopus and human cell epistasis experiments, Wnt reporter assays Science signaling High 36749823
2024 USP47 deubiquitinates and stabilizes SIRT1 protein. SIRT1 in turn upregulates PPARα expression via deacetylation, thereby promoting osteogenic differentiation of bone marrow mesenchymal stem cells via the Wnt/β-catenin pathway. Ubiquitination assay, co-immunoprecipitation, siRNA knockdown, osteogenic differentiation assays (ALP activity, Alizarin Red staining) Chemical biology & drug design Medium 38373741
2024 USP47 stabilizes IRF1 by deubiquitination, preventing its proteasomal degradation. Stabilized IRF1 binds the CXCL4 promoter to promote CXCL4 expression, which in turn promotes NLRP3 inflammasome-mediated pyroptosis and cardiac dysfunction in myocardial infarction. Co-immunoprecipitation, ubiquitination assay, luciferase reporter (IRF1-CXCL4 promoter binding), siRNA knockdown, MI mouse model International immunopharmacology Medium 38850785
2025 USP47 stabilizes c-Myc by preventing its proteasomal degradation through deubiquitination, thereby promoting NSCLC cell proliferation. USP47 inhibition destabilizes c-Myc and enhances the efficacy of the KRASG12C inhibitor Sotorasib in vitro and in vivo. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, in vitro proliferation assay, in vivo xenograft model, small molecule inhibitor (K-552) Pharmacological research Medium 40180254
2025 USP47 modulates PD-L1 protein stability through deubiquitination. USP47 interacts with PD-L1 (Co-IP) and deubiquitinates it, preventing its degradation. USP47 inhibition reduces tumoral PD-L1 levels without affecting mRNA, and combination with anti-PD-1 therapy enhanced HCC tumor suppression in mouse models. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, T cell killing assay, mouse HCC model with P5091 inhibitor International immunopharmacology Medium 40494207
2025 USP47 deubiquitinates FEN1 (flap endonuclease 1), stabilizing its protein levels. Mutant USP47 (Cys109Ser, catalytically inactive) did not stabilize FEN1. USP47 directly interacts with FEN1 (Co-IP, immunofluorescence). The natural compound rotenone physically interacts with USP47 and modulates USP47 expression and Ub-USP47 conjugation, reducing FEN1 stability. Co-immunoprecipitation, immunofluorescence, cycloheximide chase, deubiquitination assay, catalytic mutant (Cys109Ser), Biacore binding assay, xenograft model Drug design, development and therapy Medium 42112089
2025 USP47 binds, deubiquitinates, and stabilizes PRMT5 (protein arginine methyltransferase 5), thereby upregulating O-GlcNAcase expression and inhibiting O-GlcNAcylation in cardiomyocytes. This mechanism attenuates Ang II-induced cardiac hypertrophy. Co-immunoprecipitation, ubiquitination assay, adenovirus-mediated gain/loss-of-function, cardiac hypertrophy in vitro and in vivo assays Journal of cardiovascular pharmacology Medium 39436323
2025 USP47 deubiquitinates and stabilizes NRP1 (Neuropilin-1), preventing its ubiquitination and degradation, and activating the PI3K/Akt signaling pathway to promote angiogenesis in gastric cancer. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, angiogenesis assays Biochimica et biophysica acta. Molecular cell research Low 40499689
2026 USP47 directly interacts with HDAC2, promotes its deubiquitination, and enhances HDAC2 protein stability. Stabilized HDAC2 acts as a transcriptional repressor of CYP1A1 by deacetylating H3K9 and H3K27 at the CYP1A1 promoter, thereby reducing ROS-driven autophagy and protecting against cigarette smoke-induced skeletal muscle atrophy. Co-immunoprecipitation, ubiquitination assays, ChIP-qPCR, RNA-seq, gain/loss-of-function in mouse model and C2C12 cells Free radical biology & medicine Medium 41529803
2026 USP47 stabilizes SIRT1 through deubiquitination (inhibiting its ubiquitination and degradation). SIRT1 then upregulates PPARα expression via deacetylation to promote lipid metabolism and alleviate metabolic-associated fatty liver disease. SIRT1 inhibitor EX-527 reversed USP47 overexpression benefits. Co-immunoprecipitation, ubiquitination assay, rat HFD model, HepG2 OA model, gain/loss-of-function experiments, pharmacological inhibitor rescue Biochimica et biophysica acta. Molecular basis of disease Medium 41930505
2026 USP47 competitively binds ASK1 (apoptosis signal-regulating kinase 1), deubiquitinating lysine residue 805 of ASK1. NUP85 competitively displaces USP47 from ASK1, promoting ASK1 activation and exacerbating collagen deposition and endoplasmic reticulum stress in liver fibrosis. Co-immunoprecipitation, ubiquitination assay (site-specific K805), competitive binding experiments, loss-of-function in liver fibrosis model Advanced science Medium 41903125
2023 USP47 regulates cutaneous oxidative injury through stabilization of nicotinamide nucleotide transhydrogenase (NNT) by preventing its ubiquitin-mediated degradation. Loss of USP47 in mice aggravated radiation- and imiquimod-induced skin damage; knockdown of NNT increased mitochondrial ROS and disrupted mitochondrial membrane potential. Usp47 knockout mouse models, proteomic analysis, siRNA knockdown of NNT, mitochondrial ROS measurement Toxicology and applied pharmacology Medium 37924851
2025 USP47 inhibits degradation of ubiquitinated GluR1 (AMPAR subunit), thereby enhancing excitatory postsynaptic transmission and increasing dendritic spine density/maturity. Elevated USP47 was found in epileptic mice, and USP47 knockdown reduced seizure frequency and duration. Electrophysiology, dendritic spine morphology analysis, ubiquitination assay, siRNA knockdown in epileptic mouse model Neuroscience bulletin Medium 40716012

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 USP7 and USP47 deubiquitinases regulate NLRP3 inflammasome activation. EMBO reports 159 30206189
2012 Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47. ACS medicinal chemistry letters 148 24900381
2011 USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase β. Molecular cell 105 21362556
2014 MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A. Medical oncology (Northwood, London, England) 94 25429829
2015 Deubiquitinase USP47/UBP64E Regulates β-Catenin Ubiquitination and Degradation and Plays a Positive Role in Wnt Signaling. Molecular and cellular biology 78 26169834
2019 Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer letters 74 30742943
2009 The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor regulating cell survival. Oncogene 71 19966869
2021 Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia. Nature communications 61 33397955
2019 ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of βTrCP. Nature communications 50 31341163
2019 LINC00668 promotes tumorigenesis and progression through sponging miR-188-5p and regulating USP47 in colorectal cancer. European journal of pharmacology 46 31233752
2023 USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis. The Journal of clinical investigation 45 37788092
2013 USP47 and C terminus of Hsp70-interacting protein (CHIP) antagonistically regulate katanin-p60-mediated axonal growth. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 23904609
2016 The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of the N-end Rule ligase POE/UBR4 in Drosophila. PLoS biology 36 27552662
2020 Spatial transcriptomics identifies spatially dysregulated expression of GRM3 and USP47 in amyotrophic lateral sclerosis. Neuropathology and applied neurobiology 35 31925813
2020 Proteomics analysis reveals the role of ubiquitin specific protease (USP47) in Epithelial to Mesenchymal Transition (EMT) induced by TGFβ2 in breast cells. Journal of proteomics 33 32201364
2021 USP47-Mediated Deubiquitination and Stabilization of TCEA3 Attenuates Pyroptosis and Apoptosis of Colorectal Cancer Cells Induced by Chemotherapeutic Doxorubicin. Frontiers in pharmacology 31 34630087
2014 Minus end-directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions. Molecular biology of the cell 28 25253721
2021 USP47 maintains the stemness of colorectal cancer cells and is inhibited by parthenolide. Biochemical and biophysical research communications 27 34030041
2019 MicroRNA-204-5p Inhibits Ovarian Cancer Cell Proliferation by Down-Regulating USP47. Cell transplantation 26 31526052
2022 LncRNA ZNF883-Mediated NLRP3 Inflammasome Activation and Epilepsy Development Involve USP47 Upregulation. Molecular neurobiology 25 35678979
2022 USP47 stabilizes BACH1 to promote the Warburg effect and non-small cell lung cancer development via stimulating Hk2 and Gapdh transcription. American journal of cancer research 23 35141006
2021 E2F7 Transcriptionally Inhibits MicroRNA-199b Expression to Promote USP47, Thereby Enhancing Colon Cancer Tumor Stem Cell Activity and Promoting the Occurrence of Colon Cancer. Frontiers in oncology 23 33489876
2021 Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis. International journal of molecular medicine 22 33576460
2020 USP47 Promotes Tumorigenesis by Negative Regulation of p53 through Deubiquitinating Ribosomal Protein S2. Cancers 22 32370049
2020 Long non-coding RNA DSCAM-AS1 upregulates USP47 expression through sponging miR-101-3p to accelerate osteosarcoma progression. Biochemistry and cell biology = Biochimie et biologie cellulaire 22 32379981
2022 MicroRNA-101-3p Suppresses Cancer Cell Growth by Inhibiting the USP47-Induced Deubiquitination of RPL11. Cancers 21 35205710
2018 Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells. Biomedicines 21 29786670
2020 USP47 promotes apoptosis in rat myocardial cells after ischemia/reperfusion injury via NF-κB activation. Biotechnology and applied biochemistry 20 32761659
2022 Inhibition of the deubiquitinating enzyme USP47 as a novel targeted therapy for hematologic malignancies expressing mutant EZH2. Leukemia 19 35034955
2020 Gga-miR-30d regulates infectious bronchitis virus infection by targeting USP47 in HD11 cells. Microbial pathogenesis 17 31982568
2020 Deubiquitinase USP47-stabilized splicing factor IK regulates the splicing of ATM pre-mRNA. Cell death discovery 16 32377397
2023 USP47 deubiquitylates Groucho/TLE to promote Wnt-β-catenin signaling. Science signaling 13 36749823
2024 Icariin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating USP47/SIRT1/Wnt/β-catenin. Chemical biology & drug design 11 38373741
2024 Role of deubiquitinase USP47 in cardiac function alleviation and anti-inflammatory immunity after myocardial infarction by regulating NLRP3 inflammasome-mediated pyroptotic signal pathways. International immunopharmacology 11 38850785
2025 Targeting USP47 enhances the efficacy of KRAS inhibitor in KRASG12C mutated non-small cell lung cancer by controlling deubiquitination of c-Myc. Pharmacological research 8 40180254
2023 Structural and functional characterization of USP47 reveals a hot spot for inhibitor design. Communications biology 8 37740002
2023 Deubiquitinase USP47 attenuates virus-induced type I interferon signaling. International immunopharmacology 7 37001379
2023 Upregulation of ubiquitin carboxy‑terminal hydrolase 47 (USP47) in papillary thyroid carcinoma ex vivo and reduction of tumor cell malignant behaviors after USP47 knockdown by stabilizing SATB1 expression in vitro. Oncology letters 7 37564825
2025 Deubiquitinase USP47 Ameliorates Cardiac Hypertrophy Through Reducing Protein O-GlcNAcylation. Journal of cardiovascular pharmacology 5 39436323
2025 Targeting USP47 enhances immunotherapy in hepatocellular carcinoma by destabilizing PD-L1. International immunopharmacology 4 40494207
2025 USP47 Regulates Excitatory Synaptic Plasticity and Modulates Seizures in Murine Models by Blocking Ubiquitinated AMPAR Degradation. Neuroscience bulletin 4 40716012
2024 USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer. Cancer immunology, immunotherapy : CII 3 38832955
2023 Ubiquitin-specific peptidase 47 (USP47) regulates cutaneous oxidative injury through nicotinamide nucleotide transhydrogenase (NNT). Toxicology and applied pharmacology 3 37924851
2024 [Retracted] Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis. International journal of molecular medicine 1 38334226
2026 USP47 stabilizes HDAC2 to ameliorate cigarette smoke-induced skeletal muscle atrophy by suppressing CYP1A1/ROS-mediated autophagy. Free radical biology & medicine 0 41529803
2026 NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41903125
2026 USP47 alleviates metabolic-associated fatty liver disease by activating the PPARα signaling pathway through the stabilization of SIRT1. Biochimica et biophysica acta. Molecular basis of disease 0 41930505
2026 Rotenone Inhibited Osteosarcoma Cell Growth Through USP47-Induced Decreases in FEN1 Stability and DNA Integrity. Drug design, development and therapy 0 42112089
2025 USP47 enhances NRP1-mediated angiogenesis to promote gastric cancer progression. Biochimica et biophysica acta. Molecular cell research 0 40499689

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