Affinage

USP20

Ubiquitin carboxyl-terminal hydrolase 20 · UniProt Q9Y2K6

Length
914 aa
Mass
102.0 kDa
Annotated
2026-06-11
43 papers in source corpus 33 papers cited in narrative 36 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

USP20 is a USP-family deubiquitinating enzyme that removes K48- and K63-linked ubiquitin chains from a broad set of substrates to control their stability and signaling output, coupling nutrient and stress cues to metabolism, autophagy, innate immunity, and the DNA damage response (PMID:33177714, PMID:38705724). Its activity is gated by upstream phosphorylation and by counterbalancing E3 ligase activity: mTORC1 phosphorylates USP20 at S132/S134 in the fed state to recruit it to the HMGCR complex, where it deubiquitinates and stabilizes the rate-limiting cholesterol biosynthetic enzyme HMGCR (PMID:33177714), while the E3 ligase HERC2 targets USP20 for proteasomal degradation under basal conditions, an interaction relieved by ATR-mediated phosphorylation during replication stress so that USP20 can stabilize Claspin and sustain ATR-Chk1 checkpoint signaling (PMID:25355518, PMID:25326330, PMID:38570483). In innate immunity, USP20 is recruited by USP18 and directly stabilizes STING/MITA by stripping K48 chains, promoting type I interferon induction after DNA virus infection (PMID:27801882, PMID:30814308). In autophagy, USP20 stabilizes ULK1 to enable starvation-induced autophagy initiation and stabilizes the reticulophagy receptor RETREG1/FAM134B, being recruited to the ER via VAP interaction to coordinate WIPI2 recruitment (PMID:29487085, PMID:38705724). USP20 phosphorylation also tunes inflammatory signaling: PKA phosphorylation at S333 blocks DUB activity and redirects the β2-adrenergic receptor toward autophagosomal degradation rather than recycling (PMID:19424180, PMID:25666616), and IRAK1 phosphorylation at S333/S334 weakens USP20-TRAF6 association to augment K63-linked TRAF6 ubiquitination and NF-κB output (PMID:37311534). Through deubiquitination of cardiac substrates—MYH7, STAT3, NLRP3, and the HuR-GPX4 axis—USP20 governs cardiac homeostasis, hypertrophy, inflammasome activation, and ferroptosis (PMID:40192103, PMID:39365672, PMID:41042219, PMID:41921794). Across these roles USP20 acts catalytically through its active-site residues (C154/H645) on defined substrate lysines, with its ZnF-UBP and DUSP2 auxiliary domains serving as short-linear-motif-binding modules that direct substrate targeting (PMID:40192103, PMID:41042219, PMID:28091961).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2009 High

    Established USP20 as a receptor-associated deubiquitinase controlling GPCR fate, answering how an activated β2-adrenergic receptor escapes lysosomal destruction.

    Evidence Co-IP, receptor trafficking and deubiquitination assays on β2AR

    PMID:19424180

    Open questions at the time
    • Did not define the upstream signals timing USP20 dissociation/reassociation
    • Catalytic determinants on USP20 not mapped
  2. 2014 High

    Revealed that USP20 is itself a regulated node, degraded by HERC2 at baseline but stabilized by ATR phosphorylation to deubiquitinate Claspin and enforce the replication checkpoint.

    Evidence Co-IP, ubiquitination assays, phospho-mapping, checkpoint readouts in two independent labs

    PMID:25326330 PMID:25355518

    Open questions at the time
    • ATR phosphosite(s) on USP20 not precisely defined
    • Mechanism by which phosphorylation releases HERC2 unresolved
  3. 2015 High

    Showed that PKA phosphorylation at S333 is a switch that inactivates USP20 and reroutes β2AR to autophagosomal degradation, linking phosphoregulation to receptor trafficking choice.

    Evidence Site-specific phosphorylation assays, DUB activity assays, LC3-II colocalization, β2AR trafficking

    PMID:25666616

    Open questions at the time
    • Phosphatase reversing S333 not identified
    • Structural basis of activity inhibition unknown
  4. 2016 High

    Identified USP18 as a non-catalytic adaptor that recruits USP20 to deubiquitinate and stabilize STING, defining a mechanism for tuning antiviral type I IFN responses.

    Evidence Co-IP, in vitro deubiquitination, Usp18-/- MEF reconstitution, HSV-1 infection

    PMID:27801882

    Open questions at the time
    • Structural basis of the USP18-USP20-STING complex not resolved
  5. 2019 High

    Confirmed in vivo that USP20 directly stabilizes STING and is required for host antiviral defense, validated by knockout mouse susceptibility and rescue.

    Evidence Co-IP, in vivo ubiquitination, Usp20-/- mice, STING complementation

    PMID:30814308

    Open questions at the time
    • Relative contribution of USP18-dependent vs independent recruitment in vivo unclear
  6. 2017 High

    Extended USP20 substrate scope to ERK3 and structurally characterized its ZnF-UBP ubiquitin-binding domain, connecting deubiquitination to cytoskeletal/migration control.

    Evidence DUB screen, Co-IP, in vitro deubiquitination, migration assays; separate NMR domain assignment

    PMID:28091961 PMID:28167606

    Open questions at the time
    • NMR study lacked functional validation of ubiquitin binding
    • ERK3-USP20 regulation in vivo not tested
  7. 2018 Medium

    Defined USP20 roles in autophagy initiation (ULK1) and Wnt signaling (β-catenin), broadening it from receptor regulation to core homeostatic pathways.

    Evidence Co-IP, ubiquitination assays, RNAi, LC3 puncta/autophagic flux assays

    PMID:29487085 PMID:29867130

    Open questions at the time
    • β-catenin work limited to single lab, two methods
    • Ubiquitin linkage specificity on ULK1 not defined
  8. 2020 High

    Anchored USP20 to feeding-state cholesterol metabolism via mTORC1-driven S132/S134 phosphorylation and HMGCR stabilization, providing the most rigorous in vivo mechanistic model.

    Evidence Phospho-mutant knock-in and liver-specific KO mice, in vivo/in vitro ubiquitination, Co-IP

    PMID:33177714

    Open questions at the time
    • How mTORC1 accesses USP20 spatially not resolved
    • Crosstalk with other USP20 phosphosites unaddressed
  9. 2020 Medium

    Screens placed USP20 in pro-metastatic and NF-κB inflammatory programs through stabilization of SNAI2/SLUG and p62, complementing direct RIPK1 deubiquitination.

    Evidence DUB cDNA/siRNA library screens, Co-IP, ubiquitination and complex assembly assays; purified-protein in vitro DUB assay on RIPK1

    PMID:30354204 PMID:32354117 PMID:32943575

    Open questions at the time
    • Context dependence of pro- vs anti-NF-κB roles unresolved
    • SNAI2 site of deubiquitination not mapped
  10. 2023 High

    Identified IRAK1 as an IL-1β-responsive kinase phosphorylating USP20 at S333/S334 to release TRAF6 and amplify NF-κB, tying USP20 phosphoregulation to vascular inflammation in vivo.

    Evidence In vitro phosphorylation with purified IRAK1, CRISPR S334A knock-in mice, active-site probe, Co-IP/ubiquitination assays

    PMID:37311534

    Open questions at the time
    • Reconciliation with anti-NF-κB endothelial role not fully addressed
    • Phosphatase counteracting IRAK1 unknown
  11. 2024 High

    Resolved how USP20 reaches the ER and drives reticulophagy by stabilizing RETREG1/FAM134B and recruiting WIPI2, defining a spatially organized autophagy function.

    Evidence DUB screen, Co-IP, ubiquitination assays, super-resolution SIM, reticulophagy flux

    PMID:38705724

    Open questions at the time
    • Whether VAP interaction is regulated by USP20 phosphorylation unknown
  12. 2024 Medium

    Connected HERC2-USP20 regulation to autophagy in patient cells, showing p38 disrupts the interaction to elevate USP20 and stabilize ULK1.

    Evidence Co-IP, patient-derived fibroblast Western blots, lysosomal inhibition, LC3 analysis

    PMID:38570483

    Open questions at the time
    • p38 target site mediating HERC2-USP20 disruption not mapped
    • Single-lab patient-cell observations
  13. 2024 Medium

    Defined cardiac substrate MYH7, showing USP20 protects sarcomeric myosin from K48-linked degradation and prevents maladaptive hypertrophy.

    Evidence USP20-KO mice with TAC, quantitative MS, K48 ubiquitination assays, echocardiography

    PMID:39365672

    Open questions at the time
    • MYH7 ubiquitination site and responsible E3 not identified
  14. 2025 High

    Mapped catalytic and substrate-site details for cardiac substrates STAT3 (K177/H645) and NLRP3 (K243/C154), establishing USP20 as a suppressor of cardiac hypertrophy and inflammasome-driven pyroptosis.

    Evidence Co-IP/LC-MS/MS, active-site and lysine-site mutagenesis, CUT&Tag, cardiomyocyte KO and AAV9 overexpression, NLRP3-/- epistasis

    PMID:40192103 PMID:41042219

    Open questions at the time
    • How USP20 selects K63 chains on these substrates not structurally explained
  15. 2025 Medium

    Extended USP20 into RNA-binding-protein control and STING turnover in metabolic heart disease, deubiquitinating HuR (K154) to stabilize GPX4 mRNA and modulating STING via p62-dependent autophagy.

    Evidence scRNA-seq, Co-IP/LC-MS/MS, site mapping, USP20-CKO and HuR-CKO epistasis mice, AAV9; separate active-site C154 STING study in diabetic models

    PMID:41637663 PMID:41921794

    Open questions at the time
    • Dual stabilizing/degrading effects on STING context-dependence not fully reconciled
  16. 2026 Medium

    Expanded USP20 to cancer-relevant substrate stabilization (HIF1A, CTSL, GPX4) and trafficking control (RAB8A), implicating it in EMT, ferroptosis evasion, and metabolic reprogramming.

    Evidence Co-IP/MS, CUT&Tag, ubiquitination and competitive-binding assays, genetic and pharmacological inhibition, in vivo tumor models

    PMID:41049757 PMID:41261048 PMID:41651399 PMID:41844497

    Open questions at the time
    • RAB8A finding rests on single low-confidence study
    • Whether these substrates share common recruitment motifs untested
  17. 2025 Medium

    Provided a structural-rationale for substrate selectivity, defining the ZnF-UBP and DUSP2 domains as SLiM-binding modules underlying USP20/USP33 redundancy.

    Evidence Proteomic-peptide phage display, peptide arrays, NMR/ITC affinity (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • SLiM-defined targeting not validated against endogenous substrates

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single DUB integrates competing phosphorylation inputs (mTORC1, PKA, ATR, IRAK1) and SLiM-directed recruitment to choose among its many substrates in a given cell type, and whether opposing context-dependent roles (pro- vs anti-NF-κB; STING stabilization vs degradation) reflect distinct complexes or compartments.
  • No unified structural model of phosphoregulation across sites
  • Substrate-selection logic across tissues uncharacterized
  • Full-length structure with substrate engaged lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016787 hydrolase activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 2 GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-9612973 Autophagy 3 R-HSA-73894 DNA Repair 2 R-HSA-1430728 Metabolism 1 R-HSA-8953854 Metabolism of RNA 1
Partners
HERC2HMGCRRIPK1STING1TRAF6ULK1USP18VAPA
Complex memberships
HMGCR degradation complexPKCζ-RIPK1-p62 NF-κB complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 mTORC1 phosphorylates USP20 at S132 and S134 in the feeding state, recruiting USP20 to the HMGCR complex where it deubiquitinates and stabilizes HMGCR (the rate-limiting enzyme in cholesterol biosynthesis), thereby preventing its degradation. Liver-specific Usp20 deletion and USP20(S132A/S134A) knock-in mice abolish feeding-induced HMGCR stabilization. Phospho-mutant knock-in mice, liver-specific knockout, in vivo and in vitro ubiquitination assays, co-immunoprecipitation Nature High 33177714
2009 USP20 (and USP33) constitutively bind the β2-adrenergic receptor (β2AR), dissociate immediately after agonist stimulation, and reassociate upon prolonged agonist treatment to deubiquitinate the receptor, thereby redirecting it from lysosomal degradation to recycling from late-endosomal compartments and resensitizing it at the cell surface. Co-immunoprecipitation, receptor trafficking assays, deubiquitination assays The EMBO journal High 19424180
2015 Upon β2AR activation, PKAα rapidly phosphorylates USP20 on S333, which blocks USP20 deubiquitinase activity, promotes its dissociation from the activated β2AR complex, and facilitates trafficking of ubiquitinated β2ARs to autophagosomes for lysosomal degradation. Dephosphorylation of USP20 has reciprocal effects, blocking autophagosomal trafficking and promoting plasma membrane recycling. Site-specific phosphorylation assays, SDS-PAGE mobility shift, DUB activity assays, confocal colocalization with LC3-II, β2AR trafficking assays The Journal of biological chemistry High 25666616
2016 USP18 recruits USP20 to deconjugate K48-linked ubiquitin chains from STING/MITA, stabilizing STING and promoting type I IFN and proinflammatory cytokine expression after DNA virus infection. USP18 itself does not deubiquitinate STING in vitro but facilitates USP20 catalytic activity in a manner independent of USP18's own enzymatic activity. Co-immunoprecipitation, in vitro deubiquitination assay, siRNA knockdown, Usp18-/- MEF reconstitution, HSV-1 infection assays Cell research High 27801882
2019 USP20 directly interacts with STING/MITA and removes K48-linked ubiquitin chains from it, stabilizing STING and promoting antiviral signaling (IRF3 phosphorylation, IκBα phosphorylation, type I IFN induction) after HSV-1 infection. Usp20-/- mice show increased HSV-1 susceptibility; STING complementation into Usp20-/- cells fully restores antiviral signaling. Co-immunoprecipitation, in vivo ubiquitination assay, Usp20-/- mice, cell reconstitution experiments Journal of immunology High 30814308
2014 Under replication stress, ATR phosphorylates USP20, causing dissociation of the E3 ubiquitin ligase HERC2 from USP20 and stabilization of USP20. USP20 in turn deubiquitinates K48-linked polyubiquitinated Claspin, stabilizing Claspin and promoting ATR-Chk1 checkpoint signaling. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, phosphorylation assays, checkpoint activation readouts Nucleic acids research High 25355518
2014 HERC2 promotes proteasomal degradation of USP20 under unperturbed conditions. ATR-mediated phosphorylation of USP20 under replication stress dissociates HERC2 from USP20, allowing USP20 to deubiquitinate K48-linked polyubiquitinated Claspin, thereby stabilizing Claspin and promoting CHK1 phosphorylation and checkpoint activation. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, xenograft tumor models Nucleic acids research High 25326330
2018 USP20 deubiquitinates β-catenin to control its stability, thereby regulating Wnt/β-catenin signaling. USP20 knockdown increases β-catenin polyubiquitination and enhances β-catenin turnover. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, overexpression studies Cell death and differentiation Medium 29867130
2020 USP20 deubiquitinates and stabilizes SNAI2/SLUG, a metastasis-promoting transcription factor, identified through comprehensive gain- and loss-of-function DUB screens. DUB cDNA library screen, siRNA library screen, ubiquitination assays, Co-immunoprecipitation Genes & development Medium 32943575
2018 USP20 deubiquitinates and stabilizes ULK1 at basal state by removing ubiquitin moieties, preventing lysosomal degradation and maintaining ULK1 levels required for starvation-induced autophagy initiation. USP20 depletion by RNAi inhibits LC3 puncta formation (autophagic flux). Co-immunoprecipitation, ubiquitination assays, RNAi, LC3 puncta assay, autophagy flux assays EMBO reports Medium 29487085
2018 USP20 associates with components of the TNFR1 signaling pathway including RIPK1, and deubiquitinates RIPK1 in vitro (using purified USP20). In SMCs expressing dominant-negative USP20, TNF-evoked RIPK1 ubiquitination is approximately 2-fold greater, leading to increased NFκB activation. Co-immunoprecipitation, in vitro deubiquitination assay with purified USP20, transgenic/dominant-negative mouse models, siRNA knockdown Arteriosclerosis, thrombosis, and vascular biology High 30354204
2020 USP20 stabilizes p62/sequestosome-1 by deubiquitinating K48-linked polyubiquitin chains from p62, acting as a positive regulator of TNFα-mediated NFκB activation. USP20 depletion disrupts formation of the atypical PKCζ-RIPK1-p62 complex required for TNFα-mediated NFκB activation. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, complex assembly assays International journal of molecular sciences Medium 32354117
2017 USP20 interacts with and deubiquitinates ERK3 both in vitro and in intact cells, stabilizing the ERK3 protein. USP20 regulates actin cytoskeleton organization and cell migration in an ERK3-dependent manner. DUB loss-of-function screen, Co-immunoprecipitation, in vitro deubiquitination assay, siRNA knockdown, actin cytoskeleton and migration assays Molecular and cellular biology High 28167606
2024 USP20 deubiquitinates and stabilizes the reticulophagy receptor RETREG1/FAM134B by cleaving K48- and K63-linked ubiquitin chains, promoting reticulophagy under starvation. USP20 is recruited to the ER through interaction with VAPs (VAMP-associated proteins), and facilitates recruitment of WIPI2 to specific ER subdomains where USP20 and RETREG1 are enriched. DUB screen, Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, super-resolution SIM microscopy, reticulophagy flux assays Autophagy High 38705724
2021 USP20 (and USP33), as ER-associated deubiquitinases, remove ubiquitin chains from tail-anchored (TA) membrane proteins after their insertion into the ER. TA proteins are ubiquitinated by cytosolic protein quality control immediately after synthesis, but are not routed for proteasomal degradation; instead they are handed to TRC40 for ER insertion, after which USP20/33 deubiquitinate them. In vitro TA protein biogenesis assays, ubiquitination/deubiquitination assays, cell fractionation, siRNA knockdown The Journal of cell biology Medium 33792613
2023 IRAK1 is identified as a kinase that phosphorylates USP20 on Ser334 (mouse)/Ser333 (human) in response to IL-1β. This phosphorylation diminishes USP20's association with TRAF6, thereby augmenting K63-linked polyubiquitination of TRAF6 and downstream NFκB activation. USP20-S334A mice (CRISPR knock-in) associate more avidly with TRAF6 and show reduced IL-1β-induced NFκB signaling and neointimal hyperplasia. In vitro phosphorylation with purified IRAK1, siRNA knockdown of IRAK1, CRISPR/Cas9 knock-in USP20-S334A mice, active-site ubiquitin probe, Co-immunoprecipitation, ubiquitination assays The Journal of biological chemistry High 37311534
2024 HERC2 interacts with USP20, and HERC2 deficiency leads to increased USP20 protein levels. Elevated USP20 in turn stabilizes ULK1 (by deubiquitination), leading to autophagy upregulation. p38 kinase activation disrupts the HERC2-USP20 interaction, increasing USP20 and LC3-II levels. Co-immunoprecipitation, Western blot in patient-derived fibroblasts, lysosomal inhibitor experiments, LC3 analysis Cell death discovery Medium 38570483
2025 USP20 deubiquitinates STAT3 by removing K63-linked ubiquitin chains at K177 via its H645 active site, reducing STAT3 phosphorylation and nuclear translocation, thereby inhibiting STAT3 transcriptional activity at the Carm1 promoter and mitigating cardiac hypertrophy. Co-IP followed by LC-MS/MS (substrate identification), CUT&Tag sequencing, active site mutagenesis (H645), site-specific ubiquitination mapping (K177), Co-IP, USP20-KO and overexpression mouse models Advanced science High 40192103
2024 USP20 mediates deubiquitination and stabilization of MYH7 (sarcomeric myosin heavy chain 7) in cardiomyocytes; USP20-KO hearts show increased K48-linked polyubiquitination of MYH7, leading to its degradation and maladaptive eccentric hypertrophy after pressure overload. USP20-KO mice with TAC pressure overload, quantitative mass spectrometry of LV tissue, ubiquitination assays (K48), echocardiography, histology American journal of physiology. Heart and circulatory physiology Medium 39365672
2025 USP20 deubiquitinates NLRP3 by removing K63-linked ubiquitin chains at K243 via its active site C154, disrupting the interaction between NLRP3 and ASC, suppressing NLRP3 inflammasome activation and subsequent pyroptosis in cardiomyocytes. LC-MS/MS substrate identification, Co-IP, active-site mutagenesis (C154), site-specific ubiquitination mapping (K243), cardiomyocyte-specific KO mice, AAV9-mediated overexpression, NLRP3-/- mice epistasis Clinical and translational medicine High 41042219
2026 USP20 directly interacts with and deubiquitinates HIF1A (HIF-1α), preventing its proteasomal degradation and stabilizing it. USP20 co-localizes with HIF1A at target gene loci in T-ALL cells. Mass spectrometry, Co-immunoprecipitation, CUT&Tag, shRNA knockdown, USP20 inhibitor (GSK2643943A) Acta pharmaceutica Sinica. B Medium 41049757
2022 USP20 stabilizes MCL1 (anti-apoptotic Bcl-2 family member) by deubiquitinating it; USP20 depletion increases MCL1 polyubiquitination and accelerates its turnover, increasing chemotherapy sensitivity. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, Western blot in patient samples Biochemical and biophysical research communications Low 35063767
2022 USP20 deubiquitinates and stabilizes the EMT transcription factor SOX4, as demonstrated by Co-IP and deubiquitination assays; USP20 knockdown reduces SOX4 protein (but not mRNA) levels and inhibits EMT markers in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, RT-qPCR, Western blot Pathology, research and practice Low 35405623
2024 USP20 directly interacts with PTEN and prevents its degradation; USP20 overexpression rescues PTEN levels in ischemic brain injury, and PTEN inhibition abolishes USP20's neuroprotective effects, placing USP20 upstream of PTEN in ischemic signaling. Co-immunoprecipitation, Western blot, PTEN inhibitor epistasis, OGD/R cell models, MCAO mouse model International immunopharmacology Low 34953448
2021 USP20 promotes FTO protein stability by inhibiting FTO degradation, and PDIA3 enhances USP20 phosphorylation to increase FTO levels during osteogenic differentiation of preosteoblasts, forming a positive feedback regulatory loop. Co-immunoprecipitation, RNA decay assay, MeRIP, Western blot Cell biology international Low 38321831
2022 USP20 stabilizes HSPA2 via the ubiquitin-proteasome pathway; co-immunoprecipitation and mass spectrometry identified HSPA2 as a USP20 substrate, and USP20 promotes lipid accumulation in vitro through HSPA2 stabilization. Co-immunoprecipitation, mass spectrometry, immunoprecipitation, Western blot Frontiers in endocrinology Low 36636478
2024 USP20 directly interacts with YAP1 and promotes its stability by inhibiting K48-linked polyubiquitination, thereby regulating Hippo-YAP1 pathway signaling and downstream target genes in bladder cancer. siRNA screening, DUB overexpression assay, Co-immunoprecipitation, ubiquitination assays, tissue microarray Neoplasia Low 39674114
2025 USP20 directly interacts with HuR at the USP20 catalytic domain, deubiquitinates HuR at K154 by cleaving K48-linked polyubiquitin chains (preventing proteasomal degradation), and the stabilized HuR then binds GPX4 mRNA to prevent its degradation, mitigating ferroptosis and doxorubicin-induced cardiomyopathy. scRNA-seq, Co-IP/LC-MS/MS substrate identification, K154 site mapping, USP20-CKO mice, HuR-CKO mice epistasis, AAV9 overexpression International journal of biological macromolecules Medium 41921794
2026 USP20 negatively regulates RAB8A by selectively removing K48-linked polyubiquitin chains from its inactive form, thereby reducing RAB8A-dependent GLUT1 vesicular trafficking to the cell surface and glucose uptake in pancreatic cancer cells. Co-immunoprecipitation, ubiquitination assays, functional trafficking assays, in vitro and in vivo knockdown studies Cancer letters Low 41651399
2025 USP20 deubiquitinates and stabilizes STING in cardiomyocytes but promotes STING degradation through the autophagy pathway (via deubiquitination of p62) via its active site C154, thereby alleviating myocardial inflammation in diabetic cardiomyopathy. LC-MS/MS Co-IP, Co-IP, active-site mutagenesis (C154), USP20-CKO mice, db/db and HFD/STZ diabetic models FASEB journal Medium 41637663
2025 The ZnF-UBP and DUSP2 auxiliary domains of USP20 are SLiM (short linear motif)-binding domains; phage display and peptide array experiments define their consensus binding motifs, explaining functional redundancy between USP20 and USP33 for substrate targeting. Proteomic-peptide phage display, peptide arrays, affinity measurements (NMR/ITC) bioRxivpreprint Medium
2025 USP20 deubiquitinates PINK1 by hydrolyzing K48-linked polyubiquitin chains, stabilizing PINK1 protein levels and promoting CCCP-induced mitophagy. CCCP treatment accelerates USP20 deubiquitinase activity. Co-immunoprecipitation, ubiquitination assays, mitophagy flux assays, USP20 overexpression/knockdown bioRxivpreprint Low
2025 USP20 catalytic activity in endothelial cells suppresses cytokine-induced NFκB activation; phospho-mimetic USP20(S334D) increases NFκB activity, migration, and angiogenesis, while phospho-resistant USP20(S334A) reduces them. USP20 regulates MMP3 (an NFκB transcriptional target) expression, and MMP3 inhibition reduces angiogenic sprouting in Usp20-/- aortic rings. USP20-KO mice, catalytically inactive USP20 (DN) and phospho-mutant (S334A/S334D) MCECs, aortic ring assay, scratch-wound and spheroid angiogenesis assays, NFκB reporter bioRxivpreprint Medium
2026 USP20 deubiquitinates and stabilizes CTSL (cathepsin L), competing with the E3 ligase STUB1 for CTSL binding, thereby promoting EMT and cancer stem cell renewal in head and neck squamous cell carcinoma. DUB inhibitor treatment plus mass spectrometry (substrate ID), confocal colocalization, Co-immunoprecipitation, ubiquitination assays, in vitro and in vivo functional assays Clinical and translational medicine Medium 41261048
2026 USP20 deubiquitinates and stabilizes GPX4, preventing its K48-linked polyubiquitination-mediated proteasomal degradation, thereby enabling ferroptosis evasion and TKI resistance in renal cell carcinoma and lung cancer. Co-immunoprecipitation, ubiquitination assays, USP20 genetic ablation, USP20 pharmacological inhibition, in vivo tumor models Redox biology Medium 41844497
2017 The ZnF-UBP domain of USP20/VDU2 adopts a fold of three α-helices and four β-strands; NMR backbone and side-chain assignments were completed, providing structural characterization of this ubiquitin-binding domain. NMR spectroscopy (1H, 13C, 15N backbone and side-chain assignments) Biomolecular NMR assignments Low 28091961

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis. Nature 219 33177714
2009 The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. The EMBO journal 151 19424180
2016 USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA. Cell research 143 27801882
2018 USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization. Cell death and differentiation 87 29867130
2020 Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2. Genes & development 80 32943575
2014 HERC2-USP20 axis regulates DNA damage checkpoint through Claspin. Nucleic acids research 65 25355518
2023 LncRNA TINCR impairs the efficacy of immunotherapy against breast cancer by recruiting DNMT1 and downregulating MiR-199a-5p via the STAT1-TINCR-USP20-PD-L1 axis. Cell death & disease 55 36725842
2014 HERC2/USP20 coordinates CHK1 activation by modulating CLASPIN stability. Nucleic acids research 55 25326330
2018 The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation. EMBO reports 49 29487085
2018 USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 41 30354204
2015 Phosphorylation of the deubiquitinase USP20 by protein kinase A regulates post-endocytic trafficking of β2 adrenergic receptors to autophagosomes during physiological stress. The Journal of biological chemistry 38 25666616
2017 Deubiquitinating enzyme USP20 is a positive regulator of Claspin and suppresses the malignant characteristics of gastric cancer cells. International journal of oncology 32 28350092
2024 USP20 deubiquitinates and stabilizes the reticulophagy receptor RETREG1/FAM134B to drive reticulophagy. Autophagy 30 38705724
2019 USP20 Promotes Cellular Antiviral Responses via Deconjugating K48-Linked Ubiquitination of MITA. Journal of immunology (Baltimore, Md. : 1950) 29 30814308
2020 The Deubiquitinating Enzyme USP20 Regulates the TNFα-Induced NF-κB Signaling Pathway through Stabilization of p62. International journal of molecular sciences 26 32354117
2017 Deubiquitinating Enzyme USP20 Regulates Extracellular Signal-Regulated Kinase 3 Stability and Biological Activity. Molecular and cellular biology 23 28167606
2021 USP20 mitigates ischemic stroke in mice by suppressing neuroinflammation and neuron death via regulating PTEN signal. International immunopharmacology 19 34953448
2021 Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane proteins. The Journal of cell biology 14 33792613
2023 Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1β-evoked signaling in vascular smooth muscle cells and vascular inflammation. The Journal of biological chemistry 13 37311534
2022 USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis. Pathology, research and practice 13 35405623
2021 USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells. Molecular therapy oncolytics 12 34901390
2025 Cardiomyocyte Foxp1-Specific Deletion Promotes Post-injury Heart Regeneration via Targeting Usp20-HIF1ɑ-Hand1 Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 39899693
2022 The deubiquitinating enzyme USP20 regulates the stability of the MCL1 protein. Biochemical and biophysical research communications 9 35063767
2025 Cardiomyocyte-Enriched USP20 Ameliorates Pathological Cardiac Hypertrophy by Targeting STAT3 Deubiquitination. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 40192103
2017 1H, 13C and 15N backbone and side-chain resonance assignments of the ZnF-UBP domain of USP20/VDU2. Biomolecular NMR assignments 7 28091961
2025 USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination. Acta pharmaceutica Sinica. B 5 41049757
2024 A novel PDIA3/FTO/USP20 positive feedback regulatory loop induces osteogenic differentiation of preosteoblast in osteoporosis. Cell biology international 4 38321831
2024 USP20 deletion promotes eccentric cardiac remodeling in response to pressure overload and increases mortality. American journal of physiology. Heart and circulatory physiology 4 39365672
2024 Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder. Cell death discovery 3 38570483
2024 USP20 mediates malignant phenotypic changes in bladder cancer through direct interactions with YAP1. Neoplasia (New York, N.Y.) 3 39674114
2022 Sleeve gastrectomy improves lipid dysmetabolism by downregulating the USP20-HSPA2 axis in diet-induced obese mice. Frontiers in endocrinology 2 36636478
2026 Cardiomyocyte-Derived USP20 Attenuates Diabetic Cardiomyopathy by Facilitating the Degradation of STING and Mitigating STING-Mediated Inflammation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41637663
2025 UCMSCs-derived exosomal SLIT2 alleviates ischemic stroke through the β-catenin/TCF4/USP20 signaling pathway. The International journal of neuroscience 1 40272090
2025 USP20 competitively binds to STUB1 to enhance CTSL expression and promote epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Clinical and translational medicine 1 41261048
2024 [Expression and clinical significance of USP20 in oral squamous cell carcinoma]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 1 39719836
2021 Expression, purification and characterization of the second DUSP domain of deubiquitinase USP20/VDU2. Protein expression and purification 1 33529762
2026 USP20-Driven Cholesterol Metabolism Links Inflammatory Signaling to Malignancy and Stromal Coevolution in Pancreatic Cancer. Cancer research 0 41196022
2026 USP20-RAB8A signaling axis restricts pancreatic cancer progression by disrupting GLUT1 vesicular trafficking and inhibiting glucose uptake. Cancer letters 0 41651399
2026 USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination. International journal of biological sciences 0 41800264
2026 USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers. Redox biology 0 41844497
2026 Targeting ULK1 and USP20 to modulate autophagy and chemosensitivity in cancer cell lines. Biomedical reports 0 41859356
2026 Ubiquitin-specific protease 20(USP20) mitigates doxorubicin-induced cardiotoxicity by deubiquitinating and stabilizing HuR. International journal of biological macromolecules 0 41921794
2025 Cardiomyocyte USP20 alleviates septic cardiomyopathy by deubiquitinating and inhibiting NLRP3 activity. Clinical and translational medicine 0 41042219

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