Affinage

USP46

Ubiquitin carboxyl-terminal hydrolase 46 · UniProt P62068

Length
366 aa
Mass
42.4 kDa
Annotated
2026-06-11
38 papers in source corpus 26 papers cited in narrative 26 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

USP46 is a ubiquitin-specific protease whose deubiquitinating activity controls the abundance of diverse substrates, acting most broadly as a stabilizer that opposes ubiquitin-mediated degradation and tunes signaling, synaptic, and metabolic outputs (PMID:21183687, PMID:22391563, PMID:26077708). It is a histone H2A/H2B deubiquitinase active on nucleosomal substrates (PMID:21183687), and its catalytic activity is allosterically stimulated by a conserved trimeric complex with the WD40-repeat proteins WDR48 (UAF1) and WDR20 (PMID:24356955); within this complex WDR48 additionally stabilizes USP46 itself by preventing its own ubiquitination and proteasomal degradation (PMID:32587090). Through this complex USP46 deubiquitinates and stabilizes ionotropic glutamate receptors (mammalian AMPARs and C. elegans GLR-1), antagonizing their lysosomal/proteasomal turnover to control synaptic surface receptor levels and excitatory transmission (PMID:26077708, PMID:21273419, PMID:33622778), a synaptic role corroborated by loss-of-function mouse mutants that exhibit behavioral phenotypes linked to GABAergic signaling (PMID:19465912, PMID:22720038). In Wnt signaling, the USP46–UAF1–WDR20 complex deubiquitinates the co-receptor LRP6/Arrow, counteracting RNF43/ZNRF3-mediated ubiquitylation to raise cell-surface receptor levels and promote Wnt/β-catenin signaling, a function conserved from Drosophila to vertebrate organoids (PMID:37798301, PMID:37798281). In disease and cancer contexts USP46 stabilizes a wide range of substrates including the PHLPP phosphatases to suppress Akt signaling (PMID:22391563, PMID:33029497), the kinase MST1 to drive YAP1 degradation (PMID:34029571), and, when hijacked by HPV E6, Cdt2/DTL to limit Set8 and promote proliferation of transformed cells (PMID:30415951). Additional substrates documented in the corpus span HIF-1α, PTBP1, TBK1, POU4F1, BECN1, SNX5, ANK2, and CIRBP, linking USP46 to glycolytic metabolism, antiviral interferon signaling, transcription, autophagy, and ferroptosis (PMID:38176460, PMID:38522716, PMID:40328177, PMID:39909216, PMID:40251903, PMID:40589294). Loss of USP46 in podocytes causes cytosolic TDP-43 aggregation and podocyte injury, implicating it in diabetic nephropathy (PMID:41811985).

Mechanistic history

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

    Established USP46 as a physiologically important gene in the nervous system before its biochemistry was known, by linking a natural variant to behavior and GABA signaling.

    Evidence QTL mapping, congenic strains, and BAC transgenic rescue with electrophysiology and behavioral readouts in mice

    PMID:19465912

    Open questions at the time
    • Did not identify direct molecular substrates
    • Connection between the Lys92 deletion and enzymatic function not yet shown
  2. 2010 High

    Defined USP46 as a bona fide deubiquitinating enzyme acting on nucleosomal histones and identified WDR48 as a required activating partner.

    Evidence In vitro deubiquitination of nucleosomal H2A/H2B, Co-IP, and in vivo assays in Xenopus

    PMID:21183687

    Open questions at the time
    • Physiological consequences of histone deubiquitination not established
    • WDR20 not yet implicated
  3. 2011 Medium

    Connected the behavioral variant to enzymatic mechanism and revealed a neuronal substrate, showing USP46 controls glutamate receptor abundance.

    Evidence In vitro USP cleavage assay of the Lys92-deletion mutant; C. elegans genetic epistasis showing USP-46 deubiquitinates GLR-1 to block lysosomal degradation

    PMID:21273419 PMID:22043315

    Open questions at the time
    • 27% activity reduction measured with a single artificial substrate
    • Direct GLR-1 deubiquitination not reconstituted in vitro
  4. 2012 High

    Extended USP46 substrate repertoire to a tumor-suppressive axis and confirmed the GABAergic mechanism pharmacologically.

    Evidence Co-IP and in vitro deubiquitination of PHLPP with xenografts; Usp46 knockout mouse rescued by nitrazepam in a flumazenil-sensitive manner

    PMID:22391563 PMID:22720038

    Open questions at the time
    • Whether PHLPP stabilization requires the WDR cofactor complex not addressed
    • Direct molecular target underlying GABAergic phenotype not identified
  5. 2013 High

    Defined the activating trimeric complex by showing both WDR-20 and WDR-48 bind and stimulate USP-46 catalytic activity in a substrate-relevant context.

    Evidence In vitro deubiquitination activity assay, Co-IP, and C. elegans genetics with behavioral readouts

    PMID:24356955

    Open questions at the time
    • Structural basis of stimulation not resolved
    • Distinct contributions of WDR20 vs WDR48 not separated
  6. 2015 High

    Confirmed AMPAR regulation in mammals and showed USP46 can be co-opted by a viral oncoprotein complex on chromatin.

    Evidence In vitro/in vivo deubiquitination of K63-linked AMPAR chains with mEPSC recording; tandem affinity purification, Co-IP and ChIP for EBV EBNA3-WDR48/WDR20 recruitment to the p14ARF promoter

    PMID:25855980 PMID:26077708

    Open questions at the time
    • Whether EBNA3 recruitment drives histone or other substrate deubiquitination not resolved
    • Recruitment mechanism to specific AMPAR pools not defined
  7. 2018 High

    Demonstrated that high-risk HPV E6 selectively redirects USP46 to stabilize Cdt2, linking the DUB to viral oncogenesis.

    Evidence Co-IP, ubiquitination assay, shRNA knockdown, and xenograft with E6-USP46-Cdt2-Set8 epistasis

    PMID:30415951

    Open questions at the time
    • How E6 confers substrate selectivity not structurally defined
    • Role of WDR cofactors in this recruitment not tested
  8. 2020 High

    Separated the two cofactor functions, showing WDR-48 (but not WDR-20) stabilizes USP-46 protein by preventing its proteasomal degradation, and added PHLPP1/lung cancer to the substrate set.

    Evidence Ubiquitination assays, proteasome inhibitor non-additivity, WDR-48 binding-deficient point mutant, half-life measurement; separate Co-IP/ubiquitination study in lung cancer

    PMID:32587090 PMID:33029497

    Open questions at the time
    • Whether WDR-48-dependent stabilization is regulated dynamically not addressed
    • Ligase that ubiquitinates USP46 itself not identified
  9. 2021 Medium

    Broadened USP46 into Hippo-pathway tumor suppression and refined the activity-dependent regulation of synaptic receptor trafficking.

    Evidence Co-IP/ubiquitination of MST1 with YAP1 rescue in HCC; C. elegans live imaging of GLR-1 insertion and activity-regulated wdr-20 transcription

    PMID:33622778 PMID:34029571

    Open questions at the time
    • MST1 deubiquitination not reconstituted in vitro
    • Transcriptional regulator of wdr-20 not identified
  10. 2023 High

    Established a conserved role for the USP46 complex in Wnt signaling by deubiquitinating LRP6/Arrow to counteract RNF43/ZNRF3 and sustain receptor surface levels.

    Evidence Co-IP, ubiquitination assay, size exclusion chromatography, organoid viability in human cells/Xenopus/zebrafish, and independent Drosophila genetics

    PMID:37798281 PMID:37798301

    Open questions at the time
    • Mechanism of Wnt-induced complex-LRP6 association not defined
    • Whether this is selective over other receptor pools not resolved
  11. 2024 Medium

    Expanded the substrate landscape to metabolic and antiviral effectors, showing USP46 stabilizes substrates via K48-linkage removal across contexts.

    Evidence Co-IP and K48-ubiquitination assays for PTBP1 (breast cancer glycolysis/tamoxifen resistance) and the black carp TBK1 ortholog (IFN reporter assays)

    PMID:38176460 PMID:38522716

    Open questions at the time
    • TBK1 finding is in a non-mammalian ortholog
    • Cofactor dependence of these substrates not tested
  12. 2025 Medium

    Documented a wide additional substrate set linking USP46 to HIF-1α-driven glycolysis, transcription, autophagy, and ferroptosis, and mapped its in vivo brain interactome.

    Evidence Co-IP/ubiquitination assays for HIF-1α, POU4F1, BECN1, SNX5, ANK2, CIRBP with functional and in vivo models; miniTurbo-BioID knock-in mouse confirming WDR48/WDR20 and postsynaptic enrichment

    PMID:39909216 PMID:40251903 PMID:40328177 PMID:40589294 PMID:40608782 PMID:40790822 PMID:40878243

    Open questions at the time
    • Many substrates rest on single-lab Co-IP/ubiquitination without in vitro reconstitution
    • Whether each substrate requires the WDR48/WDR20 complex not systematically tested
  13. 2026 Medium

    Linked USP46 to organ-level disease by showing its loss causes pathological TDP-43 aggregation, and identified a pharmacological agonist.

    Evidence Podocyte-specific Usp46 knockout mouse, TDP-43 localization assays, acarbose treatment in a diabetic nephropathy model

    PMID:41811985

    Open questions at the time
    • Direct deubiquitination of TDP-43 by USP46 not demonstrated
    • Mechanism by which acarbose acts as a USP46 agonist not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP46 achieves substrate selectivity across its very broad reported substrate set, and which substrates genuinely require the WDR48/WDR20 complex versus context-specific recruitment, remains unresolved.
  • No structural model defining substrate-binding determinants
  • No systematic test of cofactor dependence across substrates
  • Many disease substrates rest on single-lab cellular evidence

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 2
Localization
GO:0005634 nucleus 2 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3
Partners
DTLLRP6MST1PHLPPPOU4F1TBK1WDR20WDR48
Complex memberships
USP46-UAF1(WDR48)-WDR20 deubiquitinase complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 USP12 and USP46 are histone H2A and H2B deubiquitinases that prefer nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and in vivo. WDR48, a WD40 repeat-containing protein, interacts with USP12 and USP46 and is required for their histone deubiquitination activity. In vitro deubiquitination assay with nucleosomal substrates, co-immunoprecipitation, in vivo ubiquitination assays, Xenopus overexpression/knockdown The Journal of biological chemistry High 21183687
2012 USP46 binds to PHLPP (both isoforms) and directly removes polyubiquitin chains from PHLPP in vitro and in cells, thereby stabilizing PHLPP, reducing its degradation, and suppressing Akt signaling in colon cancer cells. Co-immunoprecipitation, in vitro deubiquitination assay, ubiquitination assay in cells, shRNA knockdown, xenograft tumor models Oncogene High 22391563
2009 A 3-bp deletion causing loss of Lys92 in Usp46 is a quantitative trait variant in mice that affects immobility behavior in tail suspension and forced swimming tests, and is implicated in regulation of GABA signaling; mutant mice show decreased muscimol-induced current in hippocampal CA1 neurons and reduced GAD67 expression, rescued by BAC transgene containing wild-type Usp46. QTL mapping, congenic/subcongenic strain analysis, BAC transgenic rescue, electrophysiology, behavioral testing Nature genetics High 19465912
2015 USP46 deubiquitinates AMPA receptors (AMPARs) in vitro and in vivo, specifically removing K63-linked ubiquitin chains. Overexpression of USP46 reduces AMPAR ubiquitination, decreases AMPAR degradation, and increases surface AMPAR accumulation; knockdown elevates AMPAR ubiquitination and reduces surface AMPARs at synapses, resulting in decreased miniature excitatory postsynaptic current amplitude. In vitro deubiquitination assay, in vivo ubiquitination assay, RNAi knockdown, surface receptor assay, electrophysiology (mEPSC recording) in neurons Journal of neurochemistry High 26077708
2011 In C. elegans, the deubiquitinating enzyme USP-46 regulates glutamate receptor GLR-1 abundance in the ventral nerve cord by deubiquitinating GLR-1 and preventing its lysosomal degradation. usp-46 mutants show decreased GLR-1, increased ubiquitinated GLR-1, and GLR-1-dependent behavioral defects; blocking GLR-1 ubiquitination or lysosomal degradation suppresses the usp-46 mutant phenotype. Genetic loss-of-function mutant analysis, ubiquitination assay, genetic epistasis with ubiquitination-deficient and lysosomal degradation-deficient mutants, behavioral assays The Journal of neuroscience High 21273419
2013 The WD40-repeat proteins WDR-20 and WDR-48 bind to USP-46 and stimulate its catalytic deubiquitinating activity in vitro. In C. elegans, overexpression of WDR-20 and WDR-48 increases GLR-1 abundance and decreases ubiquitin-GLR-1 conjugates in a USP-46-dependent manner; wdr-20 and wdr-48 loss-of-function mutants show locomotion defects consistent with decreased glutamatergic signaling. In vitro deubiquitination activity assay, co-immunoprecipitation, C. elegans overexpression and loss-of-function genetics, behavioral assays, ubiquitin conjugate quantification The Journal of biological chemistry High 24356955
2011 The Lys92 deletion in USP46 reduces its deubiquitinating enzyme activity by approximately 27% compared to wild-type, as measured by USP cleavage assay using GST-Ub52 as substrate, providing molecular basis for the behavioral phenotype of mutant mice. In vitro USP cleavage assay using GST-Ub52 substrate, comparison of wild-type vs. Lys92-deletion mutant enzyme activity PloS one Medium 22043315
2012 Usp46 knockout mice exhibit short immobility in the tail suspension test comparable to the 3-bp deletion mutant, and this phenotype is reversed by the GABA-A receptor agonist nitrazepam in a flumazenil-sensitive manner, establishing that USP46 loss-of-function affects GABAergic signaling via GABA-A receptors. Usp46 knockout mouse generation, behavioral testing (TST), pharmacological manipulation with nitrazepam and flumazenil PloS one Medium 22720038
2015 The EBNA3A, EBNA3B, and EBNA3C proteins of EBV form complexes with the USP46/USP12 deubiquitination complex components WDR48, WDR20; WDR48 is the primary mediator of EBNA3 association with the DUB complex. WDR48 and USP46 are recruited to the p14(ARF) promoter in an EBNA3C-dependent manner. Tandem affinity purification, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation PLoS pathogens Medium 25855980
2018 High-risk HPV E6 oncoprotein selectively recruits the cellular deubiquitinase USP46 to deubiquitinate and stabilize Cdt2/DTL. Stabilization of Cdt2 (a component of CRL4-Cdt2 E3 ligase) limits Set8 (an epigenetic writer) levels and promotes proliferation of HPV-transformed cells. USP46 knockdown inhibits HPV-transformed tumor xenograft growth. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, xenograft tumor model, epistasis analysis (E6-USP46-Cdt2-Set8 pathway) Molecular cell High 30415951
2020 WDR-48, but not WDR-20, promotes USP-46 protein abundance by preventing its ubiquitination and proteasomal degradation. WDR-48 binding to USP-46 reduces ubiquitin-USP-46 conjugates and increases USP-46 half-life; a WDR-48 point mutant that cannot bind USP-46 fails to stabilize it. Ubiquitination assay, proteasome inhibitor treatment (nonadditive effect with WDR-48), WDR-48 point mutant analysis, siRNA knockdown in mammalian cells, in vivo C. elegans experiments, t1/2 measurement The Journal of biological chemistry High 32587090
2021 USP46 stabilizes MST1 protein in hepatocellular carcinoma cells by directly binding to it and reducing its ubiquitination, thereby increasing MST1 kinase activity, which promotes YAP1 degradation and suppresses tumor growth and metastasis. Co-immunoprecipitation, ubiquitination assay, overexpression and knockdown experiments, in vitro and in vivo proliferation/metastasis assays, epistasis (YAP1 rescue) Experimental cell research Medium 34029571
2021 WDR-20 and USP-46 work together with WDR-48 to promote surface levels of the C. elegans AMPAR GLR-1 by regulating local GLR-1 insertion into the neuronal surface. WDR-20 expression is activity-regulated: chronic reduction or increase in glutamate signaling reciprocally alters wdr-20 transcription and surface GLR-1 levels in a wdr-20-dependent manner. C. elegans genetics (loss-of-function mutants), live imaging of GLR-1 insertion rates, transcriptional reporter assays, behavioral assays, epistasis analysis The Journal of neuroscience Medium 33622778
2023 The USP46 complex (USP46, UAF1/WDR48, WDR20) deubiquitylates the Wnt co-receptor LRP6, counteracting ubiquitylation by RNF43 and ZNRF3, thereby increasing steady-state cell surface LRP6 levels and promoting Wnt/β-catenin signaling. Wnt stimulation promotes association between the USP46 complex and LRP6. USP46 is required for Wnt-dependent intestinal organoid viability. Co-immunoprecipitation, ubiquitination assay, knockdown studies, size exclusion chromatography, Xenopus and zebrafish embryo knockdown, organoid viability assay Nature communications High 37798301
2023 In Drosophila, the evolutionarily conserved Usp46-Uaf1-Wdr20 deubiquitylase complex stabilizes the Wnt co-receptor Arrow/LRP6 by reducing its ubiquitylation and turnover, increasing cell surface Arrow levels and enhancing sensitivity to Wingless morphogen signaling. Usp46 inactivation destabilizes Arrow, reduces Armadillo/β-catenin accumulation, and attenuates Wingless target gene activation, disrupting developmental patterning. Genetic loss-of-function in Drosophila, immunofluorescence for cell surface receptor levels, ubiquitination assay, target gene expression analysis, tissue patterning assays Nature communications High 37798281
2020 USP46 suppresses lung cancer cell proliferation by antagonizing the ubiquitination of PHLPP1, resulting in PHLPP1 stabilization and inhibition of AKT signaling. This was demonstrated by co-immunoprecipitation and ubiquitination assays; AKT inhibition reversed the effects of USP46 knockdown. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, AKT inhibitor epistasis, cell proliferation assay BioMed research international Medium 33029497
2024 USP46 stabilizes PTBP1 in tamoxifen-resistant breast cancer cells by inhibiting its K48-linked ubiquitination degradation, as shown by co-immunoprecipitation and ubiquitination assay. Stabilized PTBP1 increases the PKM2/PKM1 ratio, promotes glycolysis, and enhances tamoxifen resistance. Co-immunoprecipitation, K48-ubiquitination assay, USP46 overexpression/knockdown, glycolysis detection assay, drug resistance assays Biochimica et biophysica acta. Molecular basis of disease Medium 38176460
2024 In black carp, bcUSP46 interacts with bcTBK1, stabilizes TBK1 by eliminating K48-linked ubiquitination of TBK1, and enhances TBK1-mediated interferon promoter activity and antiviral gene expression. Overexpression of bcUSP46 enhances IFN pathway activation while knockdown inhibits it. Co-immunoprecipitation, immunofluorescence colocalization, K48-ubiquitination assay, overexpression/knockdown, IFN promoter reporter assay Developmental and comparative immunology Medium 38522716
2025 USP46 binds to HIF-1α, reduces its ubiquitination, and stabilizes HIF-1α protein, thereby promoting HIF-1α transcriptional activity and downstream glycolytic gene expression, which contributes to cardiac hypertrophy. USP46 knockdown decreases HIF-1α levels and glycolysis, attenuating hypertrophy. Co-immunoprecipitation, ubiquitination assay, USP46 overexpression/knockdown, metabolic profiling (lactate, pyruvate, ATP), mouse cardiac hypertrophy model Pathology, research and practice Medium 40328177
2025 USP46 interacts with and deubiquitinates SNX5 (a ferroptosis promoter) to stabilize it, thereby promoting ferroptosis in I/R-treated neuronal cells. Knockdown of SNX5 abolishes the ferroptosis-promoting effect of USP46 overexpression. Mass spectrometry for interactor identification, co-immunoprecipitation, ubiquitination assay, USP46 overexpression/knockdown, SNX5 knockdown epistasis, rat cerebral I/R model Experimental neurology Medium 39909216
2025 USP46 interacts with ANK2 (Ankyrin2) and enhances its protein stability by deubiquitination, as shown by cycloheximide chase and ubiquitination assays. Stabilized ANK2 promotes cardiomyocyte apoptosis, inflammation, and ferroptosis in myocardial infarction models; ANK2 overexpression reverses the protective effect of USP46 knockdown. Co-immunoprecipitation, cycloheximide chase assay, ubiquitination assay, USP46/ANK2 knockdown/overexpression, rat I/R model Journal of biochemical and molecular toxicology Medium 40878243
2025 USP46 interacts with CIRBP (cold-inducible RNA-binding protein) and inhibits its ubiquitination, thereby stabilizing CIRBP and sensitizing trophoblast cells to erastin-induced ferroptosis. Immunoprecipitation, ubiquitination assay, USP46 overexpression/knockdown, CIRBP rescue experiments, ferroptosis assay Integrative biology Medium 40608782
2025 USP46 interacts with the transcription factor POU4F1 via direct binding (confirmed by IP-MS, GST pull-down, and co-immunoprecipitation) and stabilizes POU4F1 by deubiquitination, increasing POU4F1 binding to the HPSE promoter, enhancing heparanase (HPSE) expression, ECM remodelling, and neural cell migration. IP-MS, GST pull-down, co-immunoprecipitation, ubiquitination assay, ChIP-qPCR, luciferase reporter assay, transwell migration assay Acta biochimica et biophysica Sinica Medium 40251903
2025 USP46 interacts with and stabilizes BECN1 by deubiquitination in prostate cancer cells, promoting autophagy and suppressing cell proliferation. Knockdown of BECN1 or autophagy inhibition partially reverses the anti-proliferative effect of USP46 overexpression. Co-immunoprecipitation, cycloheximide chase assay, BECN1 siRNA epistasis, autophagy inhibition, cell proliferation assay, xenograft model Biotechnology and applied biochemistry Medium 40589294
2025 In a knock-in mouse model expressing miniTurbo fused to endogenous Usp46, proximity labeling identified USP46-associated proteins in the adult brain including known cofactors WDR48 and WDR20. Gene Ontology analysis showed enrichment in postsynaptic pathways. PLPP3 was identified as significantly downregulated in hippocampus of Usp46-knockout mice. miniTurbo-BioID knock-in mouse, proximity-dependent biotin labeling, mass spectrometry, Usp46-knockout mouse hippocampal proteomics Experimental animals Medium 40790822
2026 Loss of USP46 in podocytes causes cytosolic translocation and aggregation of TDP-43, leading to podocyte injury. USP46 is required for podocyte homeostasis, and the drug acarbose acts as a USP46 agonist that reduces TDP-43 aggregation and protects against diabetic nephropathy. Podocyte-specific Usp46 knockout mouse, TDP-43 localization assay (fractionation/imaging), acarbose treatment, albuminuria measurement, diabetic mouse model Science translational medicine Medium 41811985

Source papers

Stage 0 corpus · 38 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
2012 The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer. Oncogene 99 22391563
2009 Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests. Nature genetics 89 19465912
2015 The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking. Journal of neurochemistry 75 26077708
2011 The deubiquitinating enzyme USP-46 negatively regulates the degradation of glutamate receptors to control their abundance in the ventral nerve cord of Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 21273419
2018 The Deubiquitinase USP46 Is Essential for Proliferation and Tumor Growth of HPV-Transformed Cancers. Molecular cell 58 30415951
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
2021 CircRNA circ-NNT mediates myocardial ischemia/reperfusion injury through activating pyroptosis by sponging miR-33a-5p and regulating USP46 expression. Cell death discovery 42 34845193
2013 The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans. The Journal of biological chemistry 39 24356955
2012 Ubiquitin-specific peptidase 46 (Usp46) regulates mouse immobile behavior in the tail suspension test through the GABAergic system. PloS one 35 22720038
2018 The novel anti-androgen candidate galeterone targets deubiquitinating enzymes, USP12 and USP46, to control prostate cancer growth and survival. Oncotarget 25 29861848
2021 Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1. Experimental cell research 24 34029571
2023 The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling. Nature communications 22 37798301
2011 Lysine 92 amino acid residue of USP46, a gene associated with 'behavioral despair' in mice, influences the deubiquitinating enzyme activity. PloS one 18 22043315
2024 USP46 enhances tamoxifen resistance in breast cancer cells by stabilizing PTBP1 to facilitate glycolysis. Biochimica et biophysica acta. Molecular basis of disease 16 38176460
2019 Ubiquitin-specific peptidase 46 (USP46) suppresses renal cell carcinoma tumorigenesis through AKT pathway inactivation. Biochemical and biophysical research communications 16 31542232
2010 Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population. Journal of human genetics 16 20111060
2022 MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma. Chemical biology & drug design 14 35637630
2017 Function of the Deubiquitinating Enzyme USP46 in the Nervous System and Its Regulation by WD40-Repeat Proteins. Frontiers in synaptic neuroscience 14 29302259
2020 USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway. BioMed research international 13 33029497
2020 The WD40-repeat protein WDR-48 promotes the stability of the deubiquitinating enzyme USP-46 by inhibiting its ubiquitination and degradation. The Journal of biological chemistry 11 32587090
2023 Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway. Cardiovascular toxicology 10 37740139
2023 The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6. Nature communications 9 37798281
2024 SP1 MEDIATES OGD/R-INDUCED CARDIOMYOCYTE INJURY VIA ENHANCING THE TRANSCRIPTION OF USP46. Shock (Augusta, Ga.) 7 38813924
2021 The WD40-Repeat Protein WDR-20 and the Deubiquitinating Enzyme USP-46 Promote Cell Surface Levels of Glutamate Receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 5 33622778
2021 miR-27a acts as an oncogene to regulate endometrial cancer progression by targeting USP46. International journal of clinical and experimental pathology 5 34239673
2019 Possible Association of the Ubiquitin-Specific Peptidase 46 Gene (USP46) with Affective Temperamental Traits in Healthy Korean Volunteers. Psychiatry investigation 3 30605993
2015 USP46: a new piece of the memory puzzle? Journal of neurochemistry 3 26237995
2025 USP46 regulates glycolysis in the process of cardiac hypertrophy through the HIF-1α pathway. Pathology, research and practice 2 40328177
2024 USP46 promotes the interferon antiviral signaling in black carp by deubiquitinating TBK1. Developmental and comparative immunology 2 38522716
2025 Heliox alleviates ischemia-reperfusion-induced damage to neuronal cells by repressing the USP46-SNX5 Axis-triggered ferroptosis. Experimental neurology 1 39909216
2025 USP46 sensitizes BeWo trophoblasts to ferroptosis by stabilizing CIRBP. Integrative biology : quantitative biosciences from nano to macro 1 40608782
2025 A novel miniTurbo knock-in mouse reveals a protein interaction network of USP46 in the brain. Experimental animals 1 40790822
2026 Acarbose ameliorates podocyte injury and glomerular lesions in diabetic nephropathy through USP46 activation. Science translational medicine 0 41811985
2025 Integrated quantitative proteomics and phosphoproteomics analysis reveals USP46-POU4F1-HPSE signaling axis in the pathogenesis of Hirschsprung disease. Acta biochimica et biophysica Sinica 0 40251903
2025 An efficient and reliable determination of hyaluronidase supports revision of the United States Pharmacopeia USP46-NF41 monograph - Hyaluronidase for injection. Journal of pharmaceutical and biomedical analysis 0 40570682
2025 The Deubiquitinating Enzyme USP46 Abolishes Cell Survival of Prostate Cancer via Enhancing BECN1-Dependent Autophagy. Biotechnology and applied biochemistry 0 40589294
2025 Inhibition of USP46/ANK2 Axis Alleviates Myocardial Infarction in Hypoxia/Reoxygenation-Treated Cardiomyocytes and Ischemia/Reperfusion-Induced Rat Models. Journal of biochemical and molecular toxicology 0 40878243

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