Affinage

USP12

Ubiquitin carboxyl-terminal hydrolase 12 · UniProt O75317

Length
370 aa
Mass
42.9 kDa
Annotated
2026-06-10
33 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP12 is a deubiquitinating enzyme that functions as the catalytic subunit of a ternary complex with the WD40-repeat scaffold UAF1 (WDR48) and the activating subunit WDR20, controlling the stability and trafficking of a broad range of substrates to regulate gene expression, cell proliferation, immune signaling, and antiviral defense (PMID:21183687, PMID:20147737). UAF1 binds USP12 at two sites with 1:2 stoichiometry, and engagement of the high-affinity fingers-subdomain interface is required for activation, while WDR20 further stimulates catalysis and, together with UAF1, governs CRM1-dependent shuttling of the complex between plasma membrane, cytoplasm, and nucleus via an N-terminal motif in USP12 and an export sequence in WDR20 (PMID:20147737, PMID:27650958, PMID:30466959); the paralog-related protein DMWD binds the same interface as WDR20 in a mutually exclusive manner and likewise activates the enzyme while differentially tuning its localization (PMID:33844468). Through nucleosomal deubiquitination of histones H2A/H2B and removal of degradative or trafficking-directed ubiquitin marks, USP12 stabilizes diverse substrates including the androgen receptor, MDM2, PHLPP1/2, BCL10, p65, p300, c-Myc, YAP, RRM2, IFI16, HMGB1, midkine, FOXO3 and Bax, and promotes Notch lysosomal degradation (PMID:21183687, PMID:22778262, PMID:24056413, PMID:24145035, PMID:29755129, PMID:33941870, PMID:35898171, PMID:37341611, PMID:37410794, PMID:38605077). In T-cell receptor signaling, USP12 deubiquitinates LAT and Trat1 to preserve the proximal TCR complex and downstream NF-κB, NFAT, and MAPK activation (PMID:26811477), and it potentiates innate and antiviral responses by stabilizing NF-κB and STING-pathway components (PMID:34381028, PMID:35898171, PMID:37410794). Independently of its catalytic activity, nuclear USP12 binds the CBP HAT domain to inhibit CBP-mediated acetylation of phospho-STAT1, sustaining nuclear p-STAT1 during interferon signaling (PMID:31899788).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2010 High

    Established that USP12 is a chromatin-directed deubiquitinase whose activity depends on an obligate partner, defining the molecular logic of substrate engagement.

    Evidence In vitro deubiquitination of nucleosomal H2A/H2B plus Xenopus knockdown and ChIP, with UAF1 co-IP showing the partner is required for activity

    PMID:21183687

    Open questions at the time
    • Did not define how UAF1 binding activates the catalytic domain
    • Range of physiological histone-modified loci not mapped
  2. 2010 High

    Identified WDR20 as a third, USP12-selective subunit, establishing the ternary architecture and showing activation is partner-specific rather than generic.

    Evidence Tandem affinity purification of the ternary complex, in vitro DUB activity assay, and siRNA depletion comparing USP12 vs USP1 complexes

    PMID:20147737

    Open questions at the time
    • Structural basis of WDR20 stimulation not resolved
    • Whether WDR20 alters substrate selection unknown
  3. 2012 High

    Showed USP12 acts on a membrane-receptor substrate to direct its trafficking fate, extending its role beyond chromatin into receptor degradation control.

    Evidence shRNA screen, in vitro DUB assay, cell-based Notch trafficking, and Drosophila homolog genetic validation

    PMID:22778262

    Open questions at the time
    • Ubiquitin linkage type on Notch not defined
    • How USP12 is targeted to endosomal Notch unknown
  4. 2013 Medium

    Linked USP12 to oncogenic signaling by showing it stabilizes the androgen receptor and the Akt phosphatase PHLPP1, positioning it as a node controlling proliferation and survival signaling.

    Evidence siRNA/TAP, co-IP, in vivo ubiquitination assays, AR transcription reporters, and Akt activity readouts

    PMID:24056413 PMID:24145035

    Open questions at the time
    • No in vitro reconstitution of AR or PHLPP1 deubiquitination
    • Single lab
  5. 2014 Medium

    Integrated the AR and PHLPP findings into a single circuit, showing USP12 dampens Akt to indirectly stabilize and activate AR.

    Evidence Co-IP, ubiquitination assays, and phospho-Akt/phospho-AR immunoblotting in prostate cancer cells

    PMID:25216524

    Open questions at the time
    • Direct vs indirect contributions to AR stability not separated
    • Single lab
  6. 2015 Medium

    Demonstrated that USP12's proliferative role requires catalytic activity, ruling out a purely scaffolding contribution to cell-cycle control.

    Evidence siRNA knockdown plus catalytically inactive C48S mutant, flow cytometry cell-cycle analysis, and qPCR of BMI-1/c-Myc/cyclin D2

    PMID:26680102

    Open questions at the time
    • Direct substrates driving G1 arrest not identified
    • Effects on transcript levels mechanistically unexplained
  7. 2016 High

    Provided the structural mechanism of activation, showing two UAF1 sites of distinct affinity and that only the high-affinity fingers interface drives catalysis.

    Evidence 2.8 Å crystal structure of USP12-Ub/UAF1, ITC, site-directed mutagenesis, and in vitro DUB activity assay

    PMID:27650958

    Open questions at the time
    • WDR20 not included in the structure
    • Function of the second, low-affinity UAF1 site unknown
  8. 2016 High

    Defined USP12 as a positive regulator of T-cell receptor signaling by identifying LAT and Trat1 as substrates protected from lysosomal degradation.

    Evidence Activity-based probe labeling in primary T cells, USP12-/- Jurkat cells with WT rescue, proximity BirA labeling, and surface TCR flow cytometry

    PMID:26811477

    Open questions at the time
    • Kinase responsible for stimulation-induced USP12 phosphorylation not identified
    • Ubiquitin linkage chemistry on LAT/Trat1 not defined
  9. 2015 Medium

    Connected the USP12/UAF1/WDR20 complex to viral transcriptional reprogramming through EBNA3 viral proteins.

    Evidence TAP/MS, co-IP, and ChIP placing WDR48 at the p14(ARF) promoter in an EBNA3C-dependent manner

    PMID:25855980

    Open questions at the time
    • USP12 and its paralog USP46 not distinguished
    • Catalytic relevance to the promoter effect untested
  10. 2018 Medium

    Expanded the prostate-cancer circuit by showing USP12 deubiquitinates MDM2 in addition to AR, embedding it in a TP53-MDM2-AR-AKT network.

    Evidence Denaturing co-IP confirming direct deubiquitination plus transcriptome analysis and immunopathology

    PMID:29755129

    Open questions at the time
    • Net directionality on p53 levels context-dependent
    • Single lab
  11. 2018 Medium

    Resolved the subcellular control of the complex, showing WDR20 recruits USP12 to the plasma membrane and CRM1-dependent export drives shuttling, dependent on defined motifs in USP12 and WDR20.

    Evidence Confocal/live microscopy of tagged proteins, mutagenesis of the USP12 N-terminal motif, and leptomycin B CRM1 inhibition

    PMID:30466959

    Open questions at the time
    • Functional consequence of each localization not directly demonstrated
    • Import machinery not identified
  12. 2020 Medium

    Revealed a catalysis-independent function of USP12 in interferon signaling, where it inhibits CBP acetyltransferase to sustain nuclear phospho-STAT1.

    Evidence Co-IP mapping USP12 to the CBP HAT domain, acetyltransferase activity assay, p-STAT1 immunoblotting, and antiviral assays

    PMID:31899788

    Open questions at the time
    • Deubiquitinase-independence not confirmed by catalytic-dead mutant in this context
    • Single lab
  13. 2021 Medium

    Established a recurring theme of USP12 stabilizing distinct substrates to control NF-κB output across immune and tumor contexts (PPM1B, BCL10, p65).

    Evidence USP12 knockout/knockdown mice, co-IP, ubiquitination assays, NF-κB reporters, and immune microenvironment/T-cell differentiation analyses

    PMID:33941870 PMID:34381028 PMID:35898171

    Open questions at the time
    • Opposing effects on NF-κB (via PPM1B vs p65/BCL10) not mechanistically reconciled
    • Ubiquitin linkage specificity varies and largely undefined
  14. 2021 Medium

    Broadened the substrate repertoire to transcriptional, survival, and angiogenic regulators (p300, HMGB1, midkine), linking USP12 to autophagy, cardiac hypertrophy, and cancer angiogenesis.

    Evidence Co-IP, ubiquitination assays, knockdown with functional rescue, and in vivo disease models

    PMID:34339675 PMID:34759262 PMID:34997217

    Open questions at the time
    • Direct vs complex-dependent deubiquitination not separated for each substrate
    • Single lab per substrate
  15. 2021 Medium

    Characterized DMWD as an alternative activating subunit binding the WDR20 interface in mutually exclusive fashion, indicating combinatorial control of activity and localization.

    Evidence Direct co-IP of tagged proteins, in vitro DUB activity assay, localization microscopy, and phylogenetic analysis

    PMID:33844468

    Open questions at the time
    • Physiological contexts favoring DMWD vs WDR20 unknown
    • Structural basis of competition not solved
  16. 2022 Medium

    Showed USP12 directly removes K63-linked ubiquitin from Bax at specific lysines, affecting half-life without proteasomal degradation, implicating it in apoptotic control.

    Evidence Yeast two-hybrid, co-IP, and site-directed mutagenesis of Bax K128/K190 with half-life assays

    PMID:36361894

    Open questions at the time
    • Cellular outcome of Bax K63 chain removal not fully defined
    • Single lab
  17. 2023 Medium

    Extended USP12 into nucleotide metabolism/replication and antiviral DNA sensing by stabilizing RRM2 and IFI16.

    Evidence Co-IP, ubiquitination assays, DNA replication stress readouts, USP12 knockout, and HSV-1 antiviral assays

    PMID:37341611 PMID:37410794

    Open questions at the time
    • Whether the same complex composition governs both substrates untested
    • Single lab per substrate
  18. 2024 Medium

    Further generalized USP12-family deubiquitination of growth/oncogenic regulators (c-Myc, YAP, FOXO3), including site-specific control of YAP K48 chains and m6A-driven upregulation of USP12.

    Evidence DUB siRNA library screens, co-IP, site-specific ubiquitination mutagenesis (YAP K315), and in vivo HCC/gastric/sepsis models

    PMID:38605077 PMID:39432777 PMID:39662205

    Open questions at the time
    • USP12 vs USP46 not distinguished for c-Myc
    • Context-determinants of substrate choice remain unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP12 achieves substrate selectivity across such a broad, context-dependent substrate range, and what dictates the choice between WDR20- vs DMWD-bound complexes and catalytic vs non-catalytic functions, remains unresolved.
  • No unifying determinant of substrate recognition identified
  • Subunit-composition rules for substrate/localization choice undefined
  • Catalysis-independent CBP inhibition not generalized beyond IFN context

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2
Partners
ARBCL10CREBBPDMWDMDM2PHLPP1WDR20WDR48
Complex memberships
USP12-UAF1(WDR48)-WDR20 deubiquitinase complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 USP12 deubiquitinates histone H2A and H2B, preferring nucleosomal substrates. WDR48 (UAF1) interacts with USP12 and is required for its histone deubiquitination activity in vitro and in vivo. In vitro deubiquitination assay with nucleosomal substrates, co-immunoprecipitation, Xenopus knockdown/overexpression with chromatin immunoprecipitation The Journal of biological chemistry High 21183687
2010 WDR20, a WD40-repeat protein, forms a ternary complex with USP12 and UAF1 (WDR48) and stimulates the enzymatic activity of the USP12×UAF1 complex but not of USP1×UAF1. Co-immunoprecipitation, tandem affinity purification of ternary complex, in vitro DUB activity assay, siRNA depletion The Journal of biological chemistry High 20147737
2012 USP12, together with its activator UAF1, deubiquitinates the non-activated form of Notch receptor in cell culture and in vitro, promoting Notch trafficking to lysosomes for degradation; USP12 silencing interrupts Notch lysosomal trafficking, increases receptor at the cell surface and elevates Notch signaling. shRNA library screen, in vitro deubiquitination assay, cell-based Notch trafficking assay, Drosophila homolog genetic validation The Journal of biological chemistry High 22778262
2013 USP12 in complex with UAF1 and WDR20 deubiquitinates the androgen receptor (AR), enhancing AR protein stability and transcriptional activity in prostate cancer cells. siRNA screen, co-immunoprecipitation, ubiquitination assay, AR stability and transcription reporter assays The Journal of biological chemistry Medium 24056413
2013 The WDR48·USP12 complex deubiquitinates PHLPP1 (PH domain leucine-rich repeat protein phosphatase 1), thereby stabilizing PHLPP1 and negatively regulating Akt activation. Tandem affinity purification, co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown with Akt activity readout The Journal of biological chemistry Medium 24145035
2014 USP12 in complex with UAF1 and WDR20 directly deubiquitinates and stabilizes the Akt phosphatases PHLPP and PHLPPL, leading to decreased pAkt levels, down-regulation of AR Ser213 phosphorylation, and enhanced AR stability and transcriptional activity. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, phospho-Akt and phospho-AR immunoblotting Oncotarget Medium 25216524
2015 USP12 regulates cell cycle progression in HeLa cells; knockdown causes G1 arrest and decreases BMI-1, c-Myc, and cyclin D2 transcript levels; catalytically inactive C48S mutant abolishes these effects, confirming dependence on deubiquitinase activity. siRNA knockdown, overexpression of WT and catalytically inactive/gain-of-function mutants, flow cytometry cell cycle analysis, qPCR Gene Medium 26680102
2015 EBNA3A and EBNA3B viral proteins associate with a deubiquitination complex containing WDR48, WDR20, and USP46 (or its paralog USP12); WDR48 is recruited to the p14(ARF) promoter in an EBNA3C-dependent manner, implicating the USP12/46 complex in EBV-mediated gene regulation. Tandem affinity purification, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation PLoS pathogens Medium 25855980
2016 Crystal structure of USP12-Ub/UAF1 complex at 2.8 Å resolution reveals two UAF1 binding sites on USP12 (1:2 stoichiometry, affinities ~4 nM and ~325 nM). Mutagenesis of the fingers subdomain shows the high-affinity interface is required for UAF1-mediated activation; the second binding site does not affect activation. X-ray crystallography, isothermal titration calorimetry, site-directed mutagenesis, in vitro DUB activity assay Journal of structural biology High 27650958
2016 TCR stimulation induces phosphorylation of Usp12 and its time-dependent translocation from nucleus to cytosol. Usp12 deubiquitylates LAT and Trat1, preventing their lysosomal degradation, thereby maintaining the proximal TCR complex and enabling NFκB, NFAT, and MAPK signaling. Activity-based probe labeling (HA-Ub-VME) in primary T cells, Usp12-/- Jurkat cells, proximity-based BirA labeling, surface TCR flow cytometry, rescue experiments with WT Usp12 Proceedings of the National Academy of Sciences of the United States of America High 26811477
2017 USP12 is required for LPS-induced NF-κB pathway activation in macrophages; USP12 knockdown reduces inhibitory phosphorylation of IκBα and attenuates LPS-induced iNOS and IL-6 expression, as well as ERK1/2 and p38 phosphorylation. siRNA knockdown in RAW 264.7 macrophages, qPCR, western blot for IκBα phosphorylation and MAPK activation Biochemical and biophysical research communications Low 28063927
2018 USP12 deubiquitinates MDM2 and AR, controlling the levels of both p53 and AR in prostate cancer; USP12 regulation of this TP53-MDM2-AR-AKT signalling network was established by denaturing immunoprecipitations and transcriptome analysis. Denaturing co-immunoprecipitation, transcriptome analysis, immunopathology Oncogene Medium 29755129
2018 WDR20 promotes recruitment of USP12 (but not USP46) to the plasma membrane; the USP12/UAF1/WDR20 complex shuttles between plasma membrane, cytoplasm, and nucleus via CRM1-dependent nuclear export. This requires a short N-terminal motif (1MEIL4) in USP12 and a nuclear export sequence in WDR20. Confocal and live microscopy of epitope-tagged proteins, site-directed mutagenesis, CRM1 inhibitor (leptomycin B) treatment European journal of cell biology Medium 30466959
2020 USP12 translocates from the cytoplasm to the nucleus upon IFN stimulation. In the nucleus, USP12 inhibits CBP acetyltransferase activity by interacting with CBP's HAT domain, blocking CBP-mediated acetylation of phospho-STAT1 and thereby inhibiting TCPTP-mediated dephosphorylation of p-STAT1, sustaining nuclear p-STAT1 and IFN antiviral efficacy. This function is independent of USP12's deubiquitinase activity. Co-immunoprecipitation (USP12–CBP interaction at HAT domain), subcellular fractionation/immunofluorescence for translocation, acetyltransferase activity assay, p-STAT1 immunoblotting, antiviral assays PLoS pathogens Medium 31899788
2021 USP12 mechanistically promotes lung tumour growth and immunosuppression through insufficient deubiquitination of PPM1B, leading to NF-κB hyperactivation in tumour cells and a pro-tumorigenic secretome. KrasG12D mouse model, USP12 knockdown/overexpression, ubiquitination assay for PPM1B, NF-κB reporter/immunoblot, immune microenvironment analysis Nature communications Medium 34381028
2021 USP12 interacts with, deubiquitylates, and stabilizes HMGB1, promoting HMGB1-mediated pro-survival autophagy in multiple myeloma and contributing to bortezomib resistance. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, autophagy flux assays, bortezomib sensitivity assays Oncogene Medium 34997217
2021 USP12 binds and stabilizes p300 by deubiquitination, thereby activating transcription of METTL3 and promoting pathological cardiac hypertrophy. Co-immunoprecipitation, ubiquitination assay, USP12 knockdown/overexpression in NRCMs, in vivo Ang II mouse model Experimental cell research Medium 34339675
2021 USP12 stabilizes BCL10 by deubiquitination, thereby activating NF-κB signaling in CD4+ T cells to promote their activation, differentiation, and proliferation; this mechanism is not observed in CD8+ T cells. USP12-deficient mice, Co-immunoprecipitation, ubiquitination assay, NF-κB reporter, T cell differentiation/proliferation assays Cell death and differentiation Medium 33941870
2021 USP12 deubiquitinates and stabilizes midkine (MDK); overexpression of MDK rescues the loss of angiogenesis caused by USP12 knockdown, establishing MDK as a functionally relevant USP12 substrate in breast cancer angiogenesis. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, MDK rescue experiments, HUVEC tube formation and migration assays, in vivo orthotopic model Cell death & disease Medium 34759262
2021 DMWD (dystrophia myotonica WD repeat protein) binds USP12 and USP46 at the same interface as WDR20, with mutually exclusive binding. Like WDR20, DMWD promotes USP12 enzymatic activity, but DMWD and WDR20 differentially modulate subcellular localization of USP12. Direct co-immunoprecipitation of epitope-tagged proteins, in vitro DUB activity assay, subcellular localization microscopy, phylogenetic/molecular evolution analysis The FEBS journal Medium 33844468
2022 USP12 deubiquitinates and stabilizes p65 (NF-κB subunit) in monocytic MDSCs, sustaining expression of iNOS and PD-L1 and thereby promoting MDSC immunosuppressive function. USP12-knockout mice, co-immunoprecipitation, ubiquitination assay, flow cytometry for iNOS/PD-L1, CD8+ T cell suppression assay Immunology Medium 35898171
2022 USP12 directly interacts with Bax and removes K63-linked ubiquitin chains from Bax (at K128 and K190), affecting Bax half-life but not proteasomal degradation. Yeast two-hybrid screening, co-immunoprecipitation, site-directed mutagenesis of Bax ubiquitination sites (K128R, K189R, K190R), protein half-life assay International journal of molecular sciences Medium 36361894
2023 USP12 directly interacts with and deubiquitinates RRM2 (ribonucleotide reductase subunit M2) in non-small cell lung cancer cells, stabilizing RRM2 protein levels; USP12 knockdown causes DNA replication stress. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, DNA replication stress assay, in vivo tumor growth assay Molecular carcinogenesis Medium 37341611
2023 USP12 deubiquitinates and stabilizes IFI16, preventing its proteasomal degradation and thereby sustaining IFI16-STING-IRF3 and p65-mediated antiviral signaling in response to HSV-1. USP12 knockout/knockdown, co-immunoprecipitation, ubiquitination assay, IFN-β/ISG expression, viral replication assay PLoS pathogens Medium 37410794
2024 WDR20 facilitates simultaneous USP12/46-mediated deubiquitination of c-Myc, maintaining c-Myc protein stability and preventing HCC cellular senescence; WDR20 silencing destabilizes c-Myc and promotes CDKN1A transcription. siRNA screen, co-immunoprecipitation, ubiquitination assay, HCC xenograft/transgenic mouse models, patient-derived organoids Proceedings of the National Academy of Sciences of the United States of America Medium 39432777
2024 USP12 deubiquitinates YAP, specifically inhibiting K48-linked poly-ubiquitination at K315, thereby stabilizing YAP and promoting gastric cancer progression via the Hippo/YAP axis; USP12 localizes to the nucleus and co-immunoprecipitates with YAP. DUB siRNA library screen, co-immunoprecipitation, immunostaining for nuclear localization, ubiquitination assay with K315 site mutagenesis, siRNA knockdown and overexpression with YAP activity readouts Cell death discovery Medium 38605077
2024 USP12 deubiquitinates FOXO3, preventing its ubiquitin-mediated degradation; elevated USP12 (stabilized by METTL3/YTHDF1-dependent m6A modification) enhances FOXO3 binding to the PUMA promoter, activating intrinsic apoptosis in sepsis-induced myocardial dysfunction. Proteomic profiling in LPS-induced mouse model, co-immunoprecipitation, ubiquitination assay, METTL3/YTHDF1 inhibitor experiments, in vitro and in vivo loss-of-function Molecular immunology Medium 39662205

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46. The Journal of biological chemistry 102 21183687
2010 WDR20 regulates activity of the USP12 x UAF1 deubiquitinating enzyme complex. The Journal of biological chemistry 81 20147737
2013 Deubiquitinating enzyme Usp12 is a novel co-activator of the androgen receptor. The Journal of biological chemistry 76 24056413
2013 WD repeat protein WDR48 in complex with deubiquitinase USP12 suppresses Akt-dependent cell survival signaling by stabilizing PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1). The Journal of biological chemistry 62 24145035
2012 The ubiquitin-specific protease 12 (USP12) is a negative regulator of notch signaling acting on notch receptor trafficking toward degradation. The Journal of biological chemistry 60 22778262
2015 The EBNA3 family of Epstein-Barr virus nuclear proteins associates with the USP46/USP12 deubiquitination complexes to regulate lymphoblastoid cell line growth. PLoS pathogens 50 25855980
2014 Deubiquitinating enzyme Usp12 regulates the interaction between the androgen receptor and the Akt pathway. Oncotarget 47 25216524
2016 Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling. Proceedings of the National Academy of Sciences of the United States of America 44 26811477
2021 USP12 downregulation orchestrates a protumourigenic microenvironment and enhances lung tumour resistance to PD-1 blockade. Nature communications 42 34381028
2018 Molecular mechanism of the TP53-MDM2-AR-AKT signalling network regulation by USP12. Oncogene 36 29755129
2022 Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1. Oncogene 35 34997217
2021 De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy. Experimental cell research 32 34339675
2016 A conserved two-step binding for the UAF1 regulator to the USP12 deubiquitinating enzyme. Journal of structural biology 29 27650958
2018 The novel anti-androgen candidate galeterone targets deubiquitinating enzymes, USP12 and USP46, to control prostate cancer growth and survival. Oncotarget 25 29861848
2020 USP12 translocation maintains interferon antiviral efficacy by inhibiting CBP acetyltransferase activity. PLoS pathogens 22 31899788
2021 USP12 promotes breast cancer angiogenesis by maintaining midkine stability. Cell death & disease 21 34759262
2021 USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10. Cell death and differentiation 19 33941870
2015 USP12 regulates cell cycle progression by involving c-Myc, cyclin D2 and BMI-1. Gene 17 26680102
2023 USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16. PLoS pathogens 16 37410794
2022 USP12 positively regulates M-MDSC function to inhibit antitumour immunity through deubiquitinating and stabilizing p65. Immunology 15 35898171
2024 WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc. Proceedings of the National Academy of Sciences of the United States of America 14 39432777
2023 Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms. Journal of translational medicine 13 37752518
2023 USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2. Molecular carcinogenesis 11 37341611
2022 Deubiquitinating Enzyme USP12 Regulates the Pro-Apoptosis Protein Bax. International journal of molecular sciences 11 36361894
2017 Deubiquitinase USP12 promotes LPS induced macrophage responses through inhibition of IκBα. Biochemical and biophysical research communications 11 28063927
2024 USP12 facilitates gastric cancer progression via stabilizing YAP. Cell death discovery 10 38605077
2023 USP12 regulates ER stress-associated osteogenesis in human periodontal ligament cells under tension stress. Cellular signalling 10 38113977
2018 WDR20 regulates shuttling of the USP12 deubiquitinase complex between the plasma membrane, cytoplasm and nucleus. European journal of cell biology 9 30466959
2020 Downregulation of USP12 inhibits tumor growth via the p38/MAPK pathway in hepatocellular carcinoma. Molecular medicine reports 8 33174033
2024 METTL3/YTHDF1-mediated m6A modification stabilizes USP12 to deubiquitinate FOXO3 and promote apoptosis in sepsis-induced myocardial dysfunction. Molecular immunology 6 39662205
2022 Grouper USP12 exerts antiviral activity against nodavirus infection. Fish & shellfish immunology 6 35032679
2024 Membrane palmitoylated protein MPP1 inhibits immune escape by regulating the USP12/ CCL5 axis in urothelial carcinoma. International immunopharmacology 4 39700963
2021 The dystrophia myotonica WD repeat-containing protein DMWD and WDR20 differentially regulate USP12 deubiquitinase. The FEBS journal 3 33844468

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