Affinage

USP46

Ubiquitin carboxyl-terminal hydrolase 46 · UniProt P62068

Length
366 aa
Mass
42.4 kDa
Annotated
2026-04-28
38 papers in source corpus 24 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP46 is a ubiquitin-specific protease that, together with its obligate cofactors WDR48/UAF1 and WDR20, removes ubiquitin from a broad spectrum of substrates to control their stability and surface abundance, thereby regulating processes including synaptic plasticity, Wnt signaling, cell proliferation, autophagy, and metabolic reprogramming. WDR48 both stimulates USP46 catalytic activity and prevents its own proteasomal degradation, while WDR20 provides additional activation; this ternary complex deubiquitinates histone H2A/H2B on nucleosomes, the Wnt co-receptor LRP6 (antagonizing RNF43/ZNRF3 E3 ligases to promote Wnt/β-catenin signaling), and AMPA-type glutamate receptors (removing K63-linked ubiquitin to maintain synaptic surface levels) (PMID:21183687, PMID:37798301, PMID:25855980, PMID:26077708, PMID:32587090). USP46 also stabilizes multiple tumor-related substrates—including PHLPP1/2 (suppressing AKT signaling), MST1 (activating Hippo pathway), and BECN1 (promoting autophagy)—positioning it as a context-dependent tumor suppressor, while its stabilization of Cdt2/DTL downstream of HPV E6, PTBP1 (driving glycolysis and tamoxifen resistance), and HIF-1α can promote oncogenic or pathological programs (PMID:22391563, PMID:34029571, PMID:22043315, PMID:30415951, PMID:38176460, PMID:40328177). In podocytes, USP46 loss causes TDP-43 cytosolic aggregation and spontaneous albuminuria, and pharmacological USP46 activation with acarbose rescues podocyte injury in diabetic nephropathy (PMID:41811985).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2010 High

    Establishing USP46 as a histone deubiquitinase and identifying WDR48 as its essential activating cofactor answered the basic question of enzymatic substrate and regulation for this poorly characterized DUB.

    Evidence In vitro deubiquitination of nucleosomal H2A/H2B, co-IP and Xenopus ChIP

    PMID:21183687

    Open questions at the time
    • Whether WDR48 acts allosterically or through substrate presentation was not resolved
    • Relative contribution of USP46 vs. USP12 to histone deubiquitination in mammalian cells unclear
  2. 2011 High

    Demonstrating that USP-46 deubiquitinates the glutamate receptor GLR-1 in C. elegans revealed the first membrane-protein substrate and linked USP46 to synaptic function and receptor trafficking.

    Evidence C. elegans usp-46 loss-of-function mutants with ubiquitination assays and genetic epistasis with lysosomal degradation pathway

    PMID:21273419

    Open questions at the time
    • Mammalian AMPAR deubiquitination by USP46 not yet tested
    • Identity of the E3 ligase opposing USP46 on GLR-1 unknown
  3. 2012 High

    Identification of PHLPP1/2 as direct USP46 substrates connected the enzyme to AKT signaling and tumor suppression, expanding its role from chromatin and synapses to cancer-relevant phosphatase regulation.

    Evidence In vitro deubiquitination, co-IP, and colon cancer xenograft assays

    PMID:22391563

    Open questions at the time
    • Whether USP46 requires WDR48/WDR20 for PHLPP deubiquitination not tested
    • Ubiquitin linkage specificity on PHLPP not determined
  4. 2013 High

    Reconstituting the trimeric USP-46–WDR-48–WDR-20 complex and showing that both WD40-repeat proteins stimulate catalytic activity defined the complete core activating machinery of this DUB.

    Evidence In vitro DUB activity assay with purified components and C. elegans genetic epistasis on GLR-1

    PMID:24356955

    Open questions at the time
    • Structural basis for WDR20-mediated activation not resolved
    • Stoichiometry of the ternary complex not determined
  5. 2015 High

    Showing that USP46 removes K63-linked ubiquitin from mammalian AMPARs and increases their surface levels and synaptic strength extended the GLR-1 finding to mammals and specified the ubiquitin chain type.

    Evidence In vitro deubiquitination, neuronal RNAi, surface biotinylation, and mEPSC electrophysiology

    PMID:26077708

    Open questions at the time
    • Whether activity-dependent regulation of USP46 modulates AMPAR levels in vivo not shown
    • Specific AMPAR subunit preferences not defined
  6. 2018 High

    Discovery that HPV E6 hijacks USP46 to stabilize Cdt2/DTL revealed the first example of a viral oncoprotein co-opting USP46, connecting the enzyme to viral pathogenesis and E3 ligase regulation.

    Evidence Co-IP, ubiquitination assay, and xenograft tumor assay in HPV-transformed cells

    PMID:30415951

    Open questions at the time
    • Whether USP46 directly binds E6 or requires an adaptor not fully resolved
    • Relevance to HPV life cycle in vivo not tested
  7. 2020 High

    Demonstrating that WDR48 stabilizes USP46 protein by preventing its own ubiquitination and proteasomal degradation established a reciprocal regulatory relationship between cofactor and enzyme.

    Evidence Proteasome inhibition, cycloheximide chase, WDR48 binding-deficient mutant analysis in mammalian cells and C. elegans

    PMID:32587090

    Open questions at the time
    • Identity of the E3 ligase targeting USP46 for degradation unknown
    • Whether WDR20 also stabilizes USP46 protein not tested
  8. 2021 Medium

    Linking USP46-mediated MST1 stabilization to Hippo-YAP pathway suppression in hepatocellular carcinoma extended USP46's tumor-suppressive reach beyond AKT to a second major growth-control pathway.

    Evidence Co-IP, ubiquitination assay, overexpression/knockdown with in vivo HCC models

    PMID:34029571

    Open questions at the time
    • No in vitro reconstitution of USP46-mediated MST1 deubiquitination
    • Whether WDR48/WDR20 are required for MST1 deubiquitination not addressed
  9. 2021 High

    Showing that WDR-20 transcription is upregulated by reduced glutamate signaling to drive USP-46-dependent local AMPAR insertion revealed a homeostatic feedback loop linking neural activity to DUB complex output.

    Evidence C. elegans genetics, GLR-1::GFP surface imaging, transcriptional reporters, and local insertion rate measurement

    PMID:33622778

    Open questions at the time
    • Whether similar transcriptional regulation of WDR20 occurs in mammalian neurons not tested
    • Transcription factors controlling wdr-20 expression not identified
  10. 2023 High

    Identifying LRP6 as a direct substrate whose deubiquitination by the USP46–WDR48–WDR20 complex opposes RNF43/ZNRF3 E3 ligases placed USP46 at the center of Wnt receptor turnover, with conservation across vertebrates and Drosophila.

    Evidence Ubiquitination assays, co-IP, Xenopus/zebrafish developmental assays, Drosophila genetics, intestinal organoids

    PMID:37798281 PMID:37798301

    Open questions at the time
    • Crystal structure of USP46 bound to LRP6 cytoplasmic domain not available
    • Tissue-specific regulation of USP46 complex in intestinal stem cells not fully defined
  11. 2025 Medium

    Conditional Usp46 knockout in podocytes causing TDP-43 aggregation and albuminuria, with pharmacological rescue by acarbose, established a non-cancer physiological role and a potential therapeutic axis for diabetic nephropathy.

    Evidence Podocyte-specific Usp46 KO mice, TDP-43 immunofluorescence, acarbose treatment in diabetic model

    PMID:41811985

    Open questions at the time
    • Direct deubiquitination of TDP-43 by USP46 not demonstrated biochemically
    • Mechanism by which acarbose activates USP46 unknown
    • Independent replication needed
  12. 2025 Medium

    In vivo proximity labeling in mouse brain confirmed the USP46–WDR48–WDR20 complex operates at postsynaptic sites and identified novel proximal proteins including PLPP3, grounding the synaptic function in native tissue.

    Evidence miniTurbo knock-in at endogenous Usp46 locus, in vivo BioID, mass spectrometry, Usp46-KO comparison

    PMID:40790822

    Open questions at the time
    • PLPP3 not validated as a direct USP46 substrate
    • Functional consequence of USP46 loss on synapse structure/function in mammalian brain not fully characterized
  13. 2025 Medium

    Multiple studies expanded USP46's substrate repertoire to include HIF-1α, POU4F1, BECN1, PTBP1, SNX5, ANK2, and CIRBP across diverse pathological contexts (cardiac hypertrophy, Hirschsprung disease, ferroptosis, tamoxifen resistance, autophagy), but most lack in vitro reconstitution with purified components.

    Evidence Co-IP and ubiquitination assays with overexpression/knockdown in cell and animal models, each from single laboratories

    PMID:38176460 PMID:39909216 PMID:40251903 PMID:40328177 PMID:40589294 PMID:40608782 PMID:40878243

    Open questions at the time
    • Most new substrates identified by single labs without independent replication
    • In vitro reconstitution of direct deubiquitination not performed for most substrates
    • Whether WDR48/WDR20 are required for each substrate interaction generally untested
    • Substrate selectivity mechanism of USP46 remains undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A structural understanding of how USP46 selects among its diverse substrates, and whether substrate specificity is dictated by the WDR48/WDR20 cofactors or by additional adaptor proteins, remains the central unresolved question.
  • No high-resolution structure of USP46 in complex with any substrate
  • Rules governing substrate selection by USP46 vs. USP12 not defined
  • Physiological roles of USP46 in most mammalian tissues unknown beyond brain, intestine, and kidney

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016787 hydrolase activity 4
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005768 endosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2 R-HSA-4839726 Chromatin organization 1 R-HSA-9612973 Autophagy 1
Partners
BECN1DTLLRP6MST1PHLPP1PHLPP2WDR20WDR48
Complex memberships
USP46–WDR48(UAF1)–WDR20

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 USP46 (and its paralog USP12) deubiquitinates both histone H2A and H2B, preferring nucleosomal substrates; WDR48 (a WD40-repeat protein) binds USP46/USP12 and is required for their histone deubiquitination activity in vitro and in vivo. In vitro deubiquitination assay with nucleosomal substrates, co-immunoprecipitation, Xenopus overexpression/knockdown with ChIP The Journal of biological chemistry High 21183687
2011 USP-46 deubiquitinates the C. elegans glutamate receptor GLR-1, preventing its lysosomal degradation and maintaining its synaptic abundance; loss of usp-46 increases ubiquitinated GLR-1 and decreases GLR-1 levels in the ventral nerve cord. Genetic loss-of-function (usp-46 mutants), ubiquitination assays, epistasis with GLR-1 ubiquitination-blocking and MVB/lysosome degradation-blocking mutations, behavioral assays The Journal of neuroscience High 21273419
2011 USP46 possesses intrinsic deubiquitinating enzyme activity cleavable against Ub52 (GST-Ub52 model substrate); deletion of Lys92 reduces this activity by ~27%, providing molecular basis for the behavioral phenotype of Usp46 mutant mice. In vitro USP cleavage assay using GST-Ub52 substrate, comparison of wild-type versus Lys92-deletion mutant USP46 PloS one Medium 22043315
2012 USP46 binds PHLPP1 and PHLPP2 and directly removes polyubiquitin chains from PHLPP in vitro and in cells, stabilizing PHLPP and leading to decreased Akt phosphorylation, reduced colon cancer cell proliferation, and decreased tumorigenesis in vivo. Co-immunoprecipitation, in vitro deubiquitination assay, ubiquitination assay in cells, knockdown/overexpression with proliferation and xenograft assays Oncogene High 22391563
2013 C. elegans WDR-20 and WDR-48 bind USP-46 and stimulate its catalytic deubiquitinating activity in vitro; overexpression of WDR-20/WDR-48 increases GLR-1 abundance and reduces ubiquitin-GLR-1 conjugates in vivo in a USP-46-dependent manner. In vitro DUB activity assay, co-immunoprecipitation, C. elegans genetics (loss-of-function and overexpression), ubiquitination assay, behavioral assays The Journal of biological chemistry High 24356955
2015 USP46 is the deubiquitinating enzyme for mammalian AMPA receptors (AMPARs); AMPARs undergo K63-linked ubiquitination, and USP46 deubiquitinates AMPARs in vitro and in vivo, reducing their degradation and increasing surface AMPAR levels and synaptic strength. In vitro deubiquitination assay, ubiquitination assays in heterologous cells and neurons, RNAi knockdown, surface biotinylation, mEPSC recording Journal of neurochemistry High 26077708
2015 The EBV nuclear proteins EBNA3A and EBNA3B associate with the USP46 deubiquitylation complex (containing WDR48 and WDR20); WDR48 mediates EBNA3 association with the DUB complex, and WDR48/USP46 are recruited to the p14(ARF) promoter in an EBNA3C-dependent manner. Tandem affinity purification, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation (ChIP) PLoS pathogens Medium 25855980
2018 The HPV high-risk E6 oncoprotein selectively recruits USP46 to deubiquitinate and stabilize Cdt2/DTL (a CRL4Cdt2 E3 ligase component); stabilized Cdt2 reduces levels of the epigenetic writer Set8, promoting HPV-transformed cell proliferation. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, xenograft tumor growth assay Molecular cell High 30415951
2018 USP46 and its paralog USP12 regulate androgen receptor (AR) protein stability and the AR-AKT-MDM2-P53 signalling pathway in prostate cancer; the anti-androgen galeterone targets USP12/USP46 to reduce full-length AR protein levels (but not AR splice variants). Small-molecule inhibition (galeterone), USP12/USP46 knockdown, Western blotting for AR/AKT/MDM2/P53, cell proliferation assays in multiple prostate cancer models Oncotarget Medium 29861848
2020 WDR-48 (WDR48/UAF1) promotes USP-46 protein stability by binding it and preventing its ubiquitination and proteasomal degradation; a WDR-48 variant with disrupted USP-46 binding cannot stabilize USP-46, indicating binding is required. Proteasome inhibition assay, ubiquitination assay of USP-46, cycloheximide chase, siRNA knockdown of wdr48, point-mutant WDR-48 analysis in mammalian cells and C. elegans The Journal of biological chemistry High 32587090
2020 USP46 stabilizes PHLPP1 by antagonizing its ubiquitination, thereby inhibiting AKT signaling and suppressing lung cancer cell proliferation; AKT inhibitor treatment reverses the proliferative effects of USP46 knockdown. Co-immunoprecipitation, ubiquitination assay, overexpression/shRNA knockdown, cell proliferation assay, AKT pathway analysis by Western blot BioMed research international Medium 33029497
2021 USP46 deubiquitinates and stabilizes MST1, leading to increased MST1 kinase activity that phosphorylates and promotes degradation of YAP1, thereby suppressing hepatocellular carcinoma cell proliferation and metastasis. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown, Western blot, in vitro and in vivo functional assays Experimental cell research Medium 34029571
2021 WDR-20 and USP-46 cooperate in an activity-dependent manner to regulate local insertion of GLR-1 (AMPAR ortholog) into the neuronal cell surface; WDR-20 transcription is upregulated by chronic reduction of glutamate signaling, providing homeostatic compensation of surface GLR-1 levels via USP-46. C. elegans genetics (loss-of-function and overexpression), GLR-1::GFP surface imaging, local insertion rate measurement, transcriptional reporters, genetic epistasis The Journal of neuroscience High 33622778
2023 The USP46–UAF1(WDR48)–WDR20 complex deubiquitylates the Wnt co-receptor LRP6, blocking its ubiquitylation by RNF43 and ZNRF3 ubiquitin ligases, increasing cell surface LRP6 levels, and promoting Wnt/β-catenin signaling; this mechanism is conserved in human cells, Xenopus, and zebrafish, and is required for Wnt-dependent intestinal organoid viability. Knockdown/overexpression, ubiquitination assay, size-exclusion chromatography, co-immunoprecipitation, Xenopus and zebrafish developmental assays, intestinal organoid assay Nature communications High 37798301
2023 The Drosophila 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 Wingless/Wnt signaling amplitude and spatial range; Usp46 loss disrupts Wingless-dependent developmental patterning and tissue homeostasis. Drosophila genetics (loss-of-function), ubiquitination assay, signaling reporter assays, immunofluorescence, epistasis with Wingless pathway components Nature communications High 37798281
2024 USP46 stabilizes PTBP1 by inhibiting its K48-linked ubiquitination and degradation; elevated PTBP1 increases the PKM2/PKM1 ratio, promotes glycolysis, and drives tamoxifen resistance in breast cancer cells. Co-immunoprecipitation, ubiquitination assay (K48-linked), overexpression/knockdown, Western blot, glycolysis assay, cell proliferation assay Biochimica et biophysica acta. Molecular basis of disease Medium 38176460
2024 The USP12/USP46-WDR48-WDR20 ternary deubiquitinating complex removes ubiquitin from the cytoplasmic tail of internalized β1 integrin (Itgb1) in early endosomes, preventing ESCRT-mediated sorting and lysosomal degradation of Itgb1 and stabilizing its cell surface levels. Genetic screen, proximity-dependent biotin identification (BioID), co-immunoprecipitation, ubiquitination assay, surface level assays bioRxivpreprint Medium
2025 USP46 binds and deubiquitinates HIF-1α, enhancing HIF-1α protein stability and transcriptional activity of downstream glycolytic enzyme genes, thereby promoting glycolysis and cardiac hypertrophy. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown in cardiomyocytes and mouse model, Western blot, metabolic profiling (lactate, pyruvate, ATP) Pathology, research and practice Medium 40328177
2025 USP46 interacts with and deubiquitinates the transcription factor POU4F1, stabilizing it; stabilized POU4F1 binds the HPSE promoter to increase heparanase expression, promoting ECM remodeling and neural cell migration relevant to Hirschsprung disease. 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 SNX5 (a ferroptosis promoter) through deubiquitination, promoting ferroptosis in ischemia/reperfusion-treated neuronal cells; SNX5 knockdown abolishes the ferroptosis-promoting effect of USP46. Mass spectrometry identification of USP46 interactors, co-immunoprecipitation, ubiquitination assay, OGD/R cell model, knockdown epistasis, rat I/R model Experimental neurology Medium 39909216
2025 USP46 loss in podocytes causes cytosolic translocation and aggregation of TDP-43; USP46-specific knockout mice develop spontaneous albuminuria. Acarbose was identified as a USP46 agonist that reduces TDP-43 aggregation and podocyte injury in diabetic nephropathy mice in a USP46-dependent manner. Podocyte-specific Usp46 knockout mice, immunofluorescence localization of TDP-43, pharmacological USP46 activation with acarbose, albuminuria measurement, in vivo diabetic model Science translational medicine Medium 41811985
2025 USP46 interacts with and deubiquitinates ANK2, enhancing ANK2 protein stability; USP46-stabilized ANK2 promotes cardiomyocyte apoptosis, inflammation, and ferroptosis in myocardial infarction models. Cycloheximide chase assay, ubiquitination assay, co-immunoprecipitation, overexpression/knockdown in H/R cell model and I/R rat model Journal of biochemical and molecular toxicology Medium 40878243
2025 USP46 interacts with and stabilizes BECN1 (beclin-1) by deubiquitination, promoting autophagy and thereby suppressing prostate cancer cell proliferation. Co-immunoprecipitation, cycloheximide chase, siRNA knockdown of BECN1, autophagy inhibition, cell proliferation and xenograft assays Biotechnology and applied biochemistry Medium 40589294
2025 USP46 interacts with CIRBP (cold-inducible RNA-binding protein) to inhibit CIRBP ubiquitination and stabilize its expression, thereby promoting erastin-induced ferroptosis in BeWo trophoblasts. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown, ferroptosis assay with erastin Integrative biology Medium 40608782
2025 In vivo proximity labeling (BioID via miniTurbo knock-in) in the mouse brain confirms that USP46 associates with known cofactors WDR48 and WDR20 in adult brain and reveals enrichment of postsynaptic proteins in the USP46 interactome; PLPP3 was identified as a novel proximal protein significantly downregulated in Usp46-KO hippocampus. miniTurbo knock-in mouse, in vivo BioID proximity labeling, mass spectrometry, Gene Ontology analysis, Usp46 knockout comparison Experimental animals Medium 40790822

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer. Oncogene 98 22391563
2010 Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46. The Journal of biological chemistry 98 21183687
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 74 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 61 21273419
2018 The Deubiquitinase USP46 Is Essential for Proliferation and Tumor Growth of HPV-Transformed Cancers. Molecular cell 57 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 49 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 41 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 34 22720038
2018 The novel anti-androgen candidate galeterone targets deubiquitinating enzymes, USP12 and USP46, to control prostate cancer growth and survival. Oncotarget 24 29861848
2021 Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1. Experimental cell research 23 34029571
2023 The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling. Nature communications 21 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
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
2024 USP46 enhances tamoxifen resistance in breast cancer cells by stabilizing PTBP1 to facilitate glycolysis. Biochimica et biophysica acta. Molecular basis of disease 15 38176460
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
2023 Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway. Cardiovascular toxicology 10 37740139
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 9 32587090
2023 The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6. Nature communications 8 37798281
2024 SP1 MEDIATES OGD/R-INDUCED CARDIOMYOCYTE INJURY VIA ENHANCING THE TRANSCRIPTION OF USP46. Shock (Augusta, Ga.) 7 38813924
2021 miR-27a acts as an oncogene to regulate endometrial cancer progression by targeting USP46. International journal of clinical and experimental pathology 5 34239673
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 4 33622778
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
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 USP46 sensitizes BeWo trophoblasts to ferroptosis by stabilizing CIRBP. Integrative biology : quantitative biosciences from nano to macro 0 40608782
2025 A novel miniTurbo knock-in mouse reveals a protein interaction network of USP46 in the brain. Experimental animals 0 40790822
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