Affinage

USP33

Ubiquitin carboxyl-terminal hydrolase 33 · UniProt Q8TEY7

Length
942 aa
Mass
106.7 kDa
Annotated
2026-06-11
51 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP33 is a deubiquitinating enzyme of the USP family that controls the stability, trafficking, and signaling output of a broad set of membrane receptors, signaling intermediates, and centrosomal proteins by removing ubiquitin conjugates to oppose proteasomal or lysosomal degradation (PMID:19424180, PMID:23486064, PMID:31432739). A founding role lies in G-protein-coupled receptor signaling: USP33 (together with USP20) constitutively associates with the beta2 adrenergic receptor, dissociates upon agonism, and deubiquitinates the receptor to inhibit lysosomal trafficking and promote recycling and resensitization (PMID:19424180), and it deubiquitinates beta-arrestin2 in reciprocal opposition to Mdm2 in a manner gated by receptor class to set signalosome stability and localization (PMID:19363159). USP33 also binds and deubiquitinates the Slit receptor Robo1, redistributing it to the plasma membrane and enabling Slit-dependent control of axon midline crossing and cell migration (PMID:19706539, PMID:19684588). In cell-cycle and organelle control, USP33 localizes to centrioles in S/G2/M and deubiquitinates CP110 to antagonize SCF(cyclin F) and regulate centrosome duplication and ciliogenesis (PMID:23486064), deubiquitinates RALB at Lys47 on starvation-induced vesicles to bias effector choice toward EXO84-beclin-1 autophagosome assembly (PMID:24056301), and acts at the outer mitochondrial membrane to deubiquitinate parkin/PRKN at Lys435, restraining its translocation and mitophagy (PMID:31432739). USP33 removes multiple chain types (K6, K11, K27, K48, K63) and shows substrate- and site-specific linkage selectivity (PMID:31432739, PMID:39256572). It stabilizes a wide range of substrates including p53 under DNA damage—loss of USP33 destabilizes p53 and sensitizes mice to hepatocarcinogenesis (PMID:39694539)—as well as DUSP1 to dampen JNK-driven apoptosis (PMID:31857702), HIF-2alpha under hypoxia downstream of ERK1/2 phosphorylation (PMID:35191554), and CBX2 via K27/K48 chain removal enhanced by GCN5 acetylation (PMID:39256572). USP33 localizes throughout the secretory pathway, with isoform-specific inserts in its catalytic domain directing ER versus Golgi targeting (PMID:21801292). Its own abundance is set by ubiquitin-dependent turnover: HERC2 polyubiquitinates USP33 and p97-Ufd1-Npl4 processes it for degradation (PMID:24855649), and beta-TrCP binds and promotes its proteasomal degradation (PMID:28506875); its catalytic activity is enhanced by CDK1 phosphorylation (PMID:40695806). The zf-UBP domain binds three zinc ions and does not bind ubiquitin (PMID:17766394).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2007 High

    Defining the structural and ubiquitin-binding properties of the USP33 zf-UBP domain established that, unlike the ubiquitin-binding zf-UBP of USP5, this auxiliary domain serves a non-canonical role.

    Evidence NMR structure determination and ubiquitin-binding assay of the USP33/VDU1 ZnF UBP domain

    PMID:17766394

    Open questions at the time
    • Did not establish what ligand the three-zinc zf-UBP domain binds
    • Functional contribution to substrate selection not tested
  2. 2008 Medium

    Identification of selenium-dependent binding to hSP56 raised the question of how cellular selenium status couples to USP33 partner interactions.

    Evidence Yeast two-hybrid screen, in vitro binding, and co-localization in LNCaP cells

    PMID:19118533

    Open questions at the time
    • Functional consequence of the interaction not established
    • No deubiquitination link demonstrated
  3. 2009 High

    A cluster of studies established USP33 as a GPCR-signaling deubiquitinase, resolving how receptor recycling, resensitization, and arrestin signalosome stability are controlled by ubiquitin removal.

    Evidence Endogenous Co-IP, receptor recycling/degradation assays, deubiquitination assays and receptor-class comparison in HEK293 (beta2AR, beta-arrestin2)

    PMID:19363159 PMID:19424180

    Open questions at the time
    • Linkage specificity of chains removed from beta2AR/beta-arrestin2 not defined
    • Structural basis of receptor-class-gated arrestin recognition unresolved
  4. 2009 High

    Demonstration that USP33 binds Robo1 and is required for Slit responsiveness extended its receptor-trafficking role into axon guidance and cell migration.

    Evidence Co-IP plus in vivo loss-of-function in chick spinal cord and breast cancer migration assays with Robo1 localization readouts

    PMID:19684588 PMID:19706539

    Open questions at the time
    • Direct deubiquitination of Robo1 chains not yet linkage-resolved here
    • Mechanism of Slit-triggered redistribution not fully defined
  5. 2011 High

    Mapping isoform-specific catalytic-domain inserts explained how USP33 splice variants partition between ER and Golgi, linking localization to function.

    Evidence GFP-isoform imaging, fractionation, and insert deletion mutagenesis

    PMID:21801292

    Open questions at the time
    • Functional consequence of differential ER vs Golgi targeting on specific substrates not tested
  6. 2013 High

    Identification of CP110 and RALB as substrates established USP33 control over centrosome duplication/ciliogenesis and over the autophagy-versus-immunity decision through effector-biased deubiquitination.

    Evidence In vitro deubiquitination with substrate-specificity controls, site mapping (RALB Lys47), cell-cycle-staged localization, effector epistasis (EXO84/SEC5), centrosome and autophagy phenotypes

    PMID:23486064 PMID:24056301

    Open questions at the time
    • How USP33 is recruited to centrioles vs RALB vesicles not defined
    • Regulation distinguishing the two functions unknown
  7. 2014 High

    Discovery of HERC2/p97 and beta-TrCP-mediated turnover answered how USP33's own abundance is set, while additional cancer studies confirmed Robo1 stabilization across tumor types.

    Evidence Quantitative MS, p97 inhibition, HERC2 identification; Co-IP and domain mapping for beta-TrCP; Robo1 stability/migration assays in colorectal and lung cancer

    PMID:24855649 PMID:24981056 PMID:25242263 PMID:28506875

    Open questions at the time
    • Conditions triggering HERC2 vs beta-TrCP-mediated degradation not delineated
    • Robo1 chain linkage not resolved in cancer contexts
  8. 2019 High

    Defining mitochondrial and cytoplasmic substrates (PRKN, DUSP1) demonstrated linkage-selective deubiquitination and placed USP33 in mitophagy and stress-kinase/apoptosis control.

    Evidence OMM fractionation, in vitro/cellular deubiquitination, PRKN Lys435 mutagenesis with K6/K11/K48/K63 linkage analysis and mitophagy assays; K48-specific DUSP1 assay with JNK/apoptosis epistasis

    PMID:31432739 PMID:31857702

    Open questions at the time
    • Determinants of multi-linkage selectivity at single sites not structurally explained
    • Whether the same active site distinguishes linkages in vivo unclear
  9. 2022 High

    Identification of HIF-2alpha as a substrate coupled to ERK1/2 phosphorylation, and of the ERAP1-ADRB2 axis, showed how upstream signaling and hepatokines modulate USP33-dependent substrate stabilization.

    Evidence Co-IP, deubiquitination assays, ERK1/2 inhibition epistasis, glioma stem cell tumor models; ADRB2 ubiquitination assay with hepatic ERAP1 manipulation in mice

    PMID:35191554 PMID:35192681

    Open questions at the time
    • Mechanism by which substrate phosphorylation enhances USP33 binding not structurally defined
    • ERAP1 effect on USP33 catalysis vs recruitment unresolved
  10. 2024 High

    In vivo demonstration that USP33 stabilizes p53 under DNA damage, and mapping of K27/K48-selective CBX2 deubiquitination tuned by acetylation, broadened its role into DNA damage responses and chromatin regulation.

    Evidence Hepatocyte-specific USP33 knockout mice with DEN hepatocarcinogenesis and DNA damage assays; proteomics/ubiquitinomics, CBX2 K277 and K199 acetylation mapping with GCN5 identification

    PMID:39256572 PMID:39694539

    Open questions at the time
    • How DNA damage signals route to USP33-p53 engagement unclear
    • Whether acetylation-enhanced recruitment generalizes to other substrates untested
  11. 2025 Medium

    Demonstration that CDK1 phosphorylates and activates USP33, and SLiM-binding profiling of its auxiliary domains, began to explain how its catalytic activity and substrate range are determined and why it overlaps with USP20.

    Evidence CDK1 kinase assay and inhibition with SIN1 deubiquitination/mTORC2 readouts; proteomic-peptide phage display and affinity measurements of zf-UBP/DUSP2 SLiM binding (preprint)

    PMID:40695806 PMID:bio_10.1101_2025.09.22.676098

    Open questions at the time
    • Phosphosite on USP33 and mechanism of activity enhancement not fully mapped
    • Direct SLiM-substrate pairings within cells not validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP33 achieves substrate selectivity, linkage discrimination at single sites, and context-dependent recruitment to distinct organelles remains the central open question.
  • No catalytic-domain co-structure with a substrate
  • Rules governing recruitment to centriole vs mitochondria vs vesicles undefined
  • Physiological hierarchy among the many reported cancer substrates unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 4
Localization
GO:0005739 mitochondrion 1 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0005815 microtubule organizing center 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-9612973 Autophagy 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-1640170 Cell Cycle 1
Partners
ADRB2ARRB2BTRCCP110HERC2PRKNRALBROBO1

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 USP33 constitutively binds beta-arrestin2 and deubiquitinates it, opposing Mdm2-mediated ubiquitination. The USP33-beta-arrestin2 interaction is regulated by receptor class: 'class A' receptors (beta2AR) promote a beta-arrestin conformation that favors USP33 binding, while 'class B' receptors (V2R) promote a conformation that disfavors it. This reciprocal regulation with Mdm2 controls the stability and subcellular localization of receptor signalosomes. Co-immunoprecipitation, deubiquitination assays, receptor trafficking assays in HEK293 cells, receptor class comparison Proceedings of the National Academy of Sciences of the United States of America High 19363159
2009 USP33 (along with USP20) constitutively associates with the beta2 adrenergic receptor (beta2AR), dissociates upon agonist stimulation, and reassociates upon prolonged treatment. This dynamic association deubiquitinates the receptor, inhibiting lysosomal trafficking and promoting recycling from late-endosomal compartments and resensitization at the cell surface. Co-immunoprecipitation of endogenous proteins, receptor recycling and degradation assays, subcellular fractionation The EMBO journal High 19424180
2009 USP33 binds the Robo1 receptor and is required for Slit-induced redistribution of Robo1 from intracellular compartments to the plasma membrane, and for Slit-dependent inhibition of directional breast cancer cell migration. Co-immunoprecipitation, USP33 knockdown/rescue, cell migration assays, immunofluorescence localization of Robo1 Proceedings of the National Academy of Sciences of the United States of America High 19706539
2009 USP33 interacts with the Robo1 receptor and is essential for commissural axon midline crossing and Slit responsiveness in vertebrate neural development. Co-immunoprecipitation, in vivo loss-of-function in chick embryo spinal cord, axon guidance assays Nature neuroscience High 19684588
2007 The ZnF UBP domain of USP33/VDU1 was solved by NMR spectroscopy. Unlike the related USP5 ZnF UBP domain, the USP33 ZnF UBP domain contains three zinc ions and does not bind ubiquitin. NMR spectroscopy, structure determination, ubiquitin-binding assay Protein science : a publication of the Protein Society High 17766394
2013 USP33 interacts with and specifically deubiquitinates CP110 (a centriolar protein), but not other cyclin-F substrates. USP33 localizes to centrioles primarily in S and G2/M phases and antagonizes SCF(cyclin F)-mediated ubiquitination of CP110, thereby regulating centrosome duplication and ciliogenesis. USP33 ablation destabilizes CP110 and inhibits centrosome amplification. Co-immunoprecipitation, in vitro deubiquitination assay, cell-cycle-staged immunofluorescence localization, RNAi knockdown with centrosome/ciliogenesis phenotype readout, specificity comparison with other cyclin-F substrates Nature High 23486064
2013 USP33 accumulates on RALB-positive vesicles upon nutrient starvation and deubiquitylates RALB at Lys47. Deubiquitylated RALB preferentially interacts with EXO84 to drive RALB-EXO84-beclin-1 complex assembly and autophagosome formation, while ubiquitylated RALB favors SEC5 binding for innate immunity signaling. Ubiquitylation site mapping (Lys47), Co-immunoprecipitation, vesicle localization by immunofluorescence, epistasis experiments with EXO84/SEC5 effectors, autophagy assays Nature cell biology High 24056301
2014 USP33 deubiquitinates and stabilizes Robo1 in colorectal cancer cells, mediating the inhibitory effect of Slit2 on CRC cell migration. Co-immunoprecipitation, ubiquitination assay, USP33 knockdown with Robo1 protein stability readout, cell migration assays International journal of cancer Medium 25242263
2014 USP33 mediates Slit-Robo signaling in lung cancer cells by stabilizing Robo1 protein; USP33 downregulation reduces Robo1 protein stability. Protein stability assay, USP33 knockdown, cell migration assays Protein & cell Medium 24981056
2014 USP33 degradation is controlled by the ubiquitin-proteasome system: the E3 ligase HERC2 polyubiquitinates USP33, and the p97 ATPase (with its Ufd1-Npl4 adaptor complex) is required for post-ubiquitination processing and degradation of USP33. Quantitative mass spectrometry, p97 knockdown/chemical inhibition, HERC2 identification, accumulation of polyubiquitinated USP33 upon p97 inhibition The Journal of biological chemistry High 24855649
2011 USP33 localizes broadly to the secretory pathway (ER-associated structures) in all splice variants. A specific insert within the catalytic domain mediates ER association, while a second insert suppresses Golgi localization; splice variant 3 excises eight amino acids from this second insert, enabling marked accumulation at the Golgi apparatus. GFP-USP33 isoform expression and live/fixed imaging, subcellular fractionation, domain deletion/insert mutagenesis, endogenous USP33 localization Traffic (Copenhagen, Denmark) High 21801292
2019 USP33 localizes to the outer mitochondrial membrane and deubiquitinates PRKN/parkin in a DUB-activity-dependent manner, preferentially removing K6, K11, K48, and K63-linked ubiquitin conjugates at Lys435 of PRKN. USP33 knockdown increases K63-linked PRKN ubiquitination under mitochondrial depolarization and enhances PRKN translocation to depolarized mitochondria, promoting mitophagy. Subcellular fractionation, Co-immunoprecipitation, in vitro and cellular deubiquitination assays, linkage-specific ubiquitin analysis, site-directed mutagenesis (Lys435), mitophagy assays Autophagy High 31432739
2019 USP33 interacts with and stabilizes the phosphatase DUSP1 by inhibiting K48-linked polyubiquitination of DUSP1, thereby negatively regulating JNK activation and apoptosis in docetaxel-treated prostate cancer cells. Co-immunoprecipitation, ubiquitination assay (K48-linkage specific), JNK inhibitor rescue, USP33 knockdown/knockout with apoptosis and JNK phosphorylation readouts Cell death and differentiation High 31857702
2008 USP33/VDU1 interacts with human selenium-binding protein-1 (hSP56) in a selenium-dependent manner; specifically, the full-length VDU1 binds the selenium-replete form of hSP56. The two proteins co-localize in the perinuclear region of LNCaP cells. Yeast two-hybrid screen, in vitro binding assay, subcellular co-localization by immunofluorescence Biochemical and biophysical research communications Medium 19118533
2020 USP33 stabilizes the transcription factor SP1 by directly binding it and decreasing its ubiquitination, thereby upregulating c-Met expression in hepatocellular carcinoma cells. Co-immunoprecipitation, ubiquitination assay, RNA sequencing, luciferase reporter assay, USP33 knockdown with SP1 stability and c-Met expression readouts Life sciences Medium 32835698
2022 USP33 interacts with HIF-2alpha and deubiquitinates it to promote its stabilization in glioma stem cells, particularly under hypoxia. ERK1/2 activation upon hypoxia phosphorylates HIF-2alpha, enhancing its interaction with USP33. USP33 silencing disrupts glioma stem cell maintenance, reduces tumor vascularization, and inhibits glioblastoma growth. Co-immunoprecipitation, deubiquitination assay, USP33 knockdown, ERK1/2 inhibition epistasis, in vitro and in vivo tumor models The EMBO journal High 35191554
2017 The E3 ubiquitin ligase β-TrCP interacts with USP33 (requiring the WD40 motif of β-TrCP and amino acids 201-400 of USP33) independently of the classic β-TrCP binding motif, and promotes USP33 degradation via the ubiquitin-proteasome pathway. Co-immunoprecipitation, domain mapping, proteasome inhibitor rescue, USP33 protein level assay upon β-TrCP manipulation Experimental cell research Medium 28506875
2020 USP33 stabilizes ATF3 protein via deubiquitylation; reduced USP33 in human microglia decreases ATF3 stability, leading to elevated proinflammatory signaling (TNF-α, NF-κB, IFN-β). This pathway is exploited by dengue virus via EV-delivered miR-148a that suppresses USP33 expression. In vivo ubiquitination assay, chase assay, knockdown/overexpression, dual luciferase reporter assay, immunoblotting Journal of immunology (Baltimore, Md. : 1950) Medium 32848034
2021 USP33 regulates the turnover of IRF9 via deubiquitylation; reduced USP33 (caused by SARS-CoV-2 Spike-induced exosomal miR-148a suppression) decreases IRF9 stability and promotes neuroinflammation in human microglia. Knockdown/overexpression, miRNA mimic/inhibitor, immunoblotting for IRF9 protein levels as readout of USP33-dependent deubiquitylation Frontiers in immunology Low 33936086
2018 USP33 deubiquitinates PPM1A (a Smad2/3 phosphatase), and this activity is required to restrain TGF-β/Smad2/3 signaling and radiation-induced EMT in lung cancer cells. Luciferase 3'UTR assay (validating USP33 as miR-3591-5p target), western blot for Smad2/3 phosphorylation, USP33/PPM1A rescue experiments Cellular physiology and biochemistry Medium 30308513
2021 USP33 deubiquitinates and stabilizes c-Myc in prostate cancer cells, and this activity is regulated via a circ_0057558/miR-206/USP33 axis. Co-immunoprecipitation, deubiquitination assay for c-Myc, luciferase reporter assay, RNA pulldown for miR-206/circ_0057558 interaction Frontiers in cell and developmental biology Medium 33718387
2023 USP33 interacts with TGFBR2 (TGF-beta receptor 2), deubiquitinates it, and prevents its lysosomal degradation, thereby promoting TGFBR2 membrane accumulation and sustained TGF-β signaling. ZEB1, a TGF-β target, in turn transcriptionally upregulates USP33, forming a positive feedback loop. Mass spectrometry substrate screen, luciferase complementation assay, Co-IP, ubiquitination assay, lysosome inhibitor rescue, USP33 knockdown/overexpression Cell death & disease Medium 37322017
2023 USP33 interacts with CTNNB1 (beta-catenin) and suppresses its ubiquitin-mediated degradation, stabilizing CTNNB1 and promoting pancreatic cancer cell survival and stemness. Co-immunoprecipitation, ubiquitination assay, CTNNB1 rescue experiments, cell proliferation and sphere formation assays Cell biology international Medium 37076992
2023 USP33 stabilizes PFKFB3 by suppressing ubiquitin-mediated degradation of PFKFB3, driving aerobic glycolysis in osteosarcoma cells. Co-immunoprecipitation, ubiquitination assay, USP33 knockdown with PFKFB3 protein stability and glycolysis readouts American journal of cancer research Medium 37034227
2023 USP33 catalyzes deubiquitination of JAK2, activating JAK2/STAT3 signaling; this is the mechanistic basis for USP33-driven inflammatory injury in LPS-treated cardiomyocytes. Co-immunoprecipitation, ubiquitination assay, dual luciferase reporter (miR-206 target validation), USP33/JAK2 rescue epistasis Molecular and cellular biochemistry Medium 37256445
2024 USP33 removes K27- and K48-linked ubiquitin chains from CBX2 at Lys277, stabilizing CBX2. Acetylation of CBX2 at K199 by GCN5 enhances its interaction with USP33 and promotes further deubiquitination. Proteomics and ubiquitinomics substrate screen, Co-immunoprecipitation, ubiquitin linkage-specific assays, acetylation mapping, GCN5 identification Oncogene High 39256572
2024 USP33 interacts with and deubiquitinates TRAF3 to upregulate its expression, and USP33-TRAF3 activates the NF-κB pathway in pancreatic ductal cells during acute pancreatitis. Co-immunoprecipitation, ubiquitination assay, immunofluorescence co-localization, USP33 knockdown with TRAF3 ubiquitination and NF-κB pathway readouts Shock (Augusta, Ga.) Medium 39637362
2024 USP33 interacts with, deubiquitinates, and stabilizes integrin α6, mediating laminin-dependent adhesion, spreading, and migration of esophageal squamous cell carcinoma cells. Co-immunoprecipitation, deubiquitination assay, USP33 knockdown with integrin α6 stability, adhesion/migration, and in vivo metastasis readouts Journal of cancer research and clinical oncology Medium 39589547
2024 USP33 stabilizes p53 by directly interacting with it and mediating its deubiquitination under DNA damage conditions. USP33 depletion increases p53 ubiquitination, destabilizes p53, impairs DNA damage responses (cell cycle arrest and apoptosis), and increases sensitivity to hepatocarcinogenesis in vivo in hepatocyte-specific USP33 knockout mice. Co-immunoprecipitation, in vitro and cellular deubiquitination assays, USP33 knockout (cell lines and hepatocyte-specific mouse), DNA damage response assays, DEN-induced hepatocarcinogenesis model Cell proliferation High 39694539
2025 USP33 deubiquitinates and stabilizes SIN1 (an mTORC2 component), promoting mTORC2-AKT pathway activation and chemoresistance in pancreatic cancer. CDK1 directly phosphorylates USP33, enhancing its deubiquitinase activity toward SIN1. Co-immunoprecipitation, ubiquitination assay, CDK1 phosphorylation assay, CDK1 inhibition/genetic ablation, USP33 knockdown, in vivo tumor models Cell death & disease Medium 40695806
2025 USP33 stabilizes TAP63 through K48-linked deubiquitination in triple-negative breast cancer cells, triggering autophagy and ferroptosis. Co-immunoprecipitation, ubiquitin chain analysis (K48-linkage), autophagy/ferroptosis assays (fluorescence probes, electron microscopy, biomarkers), in vivo xenograft Cellular and molecular life sciences : CMLS Medium 40801947
2022 The hepatokine ERAP1 interacts with beta2 adrenergic receptor (ADRB2) and reduces its expression by decreasing USP33-mediated deubiquitination of ADRB2, thereby impairing ADRB2-stimulated insulin signaling in skeletal muscle. Co-immunoprecipitation, ADRB2 ubiquitination assay, USP33 knockdown, hepatic ERAP1 overexpression/knockdown in mice Diabetes Medium 35192681
2025 USP33 interacts with TRAF2 and stabilizes it through deubiquitination in pulmonary microvascular endothelial cells, promoting HPMEC pyroptosis during acute lung injury. Co-immunoprecipitation, ubiquitination assay, USP33 knockdown with pyroptosis and TRAF2 stability readouts Histology and histopathology Low 39506557
2025 USP33 deubiquitinates and stabilizes eEF1A1, preventing its ubiquitin-mediated degradation, which in turn promotes ILEI protein synthesis and EMT in hepatocellular carcinoma. CRISPR knockout screen, transcriptome sequencing, proteomic analysis, Co-immunoprecipitation, ubiquitination assay International journal of biological macromolecules Medium 42144151
2025 USP33 deubiquitinates c-Myc at K48-linked chains, stabilizing c-Myc and enhancing glycolytic metabolism in ovarian cancer cells. Co-immunoprecipitation, K48-linkage specific ubiquitination assay, c-Myc rescue experiments, glycolysis assays Biochimica et biophysica acta. General subjects Medium 40532745
2025 USP33 interacts with and deubiquitinates CNR1 (cannabinoid receptor 1), promoting its stabilization and OPC differentiation via AKT/mTOR pathway activation in chronic cerebral hypoperfusion. Co-immunoprecipitation, ubiquitination assay, USP33 overexpression, in vivo BCAS model Neuroscience bulletin Low 40679549
2026 USP33 interacts with ATG7 and blocks K63-linked ubiquitination at ATG7 K48 (mouse K44), stabilizing ATG7. This USP33-ATG7 interaction promotes lysosomal degradation of FIS1 (a mitochondrial fission protein) via ATG7-mediated autophagy, thereby suppressing excessive FIS1-dependent mitochondrial fission in diabetic cardiomyopathy. DUB-targeting library screen, Co-immunoprecipitation, K63-linkage specific ubiquitination assay, USP33 silencing with FIS1 and mitochondrial function readouts Cell death & disease Medium 42218158
2025 USP33 deubiquitinates PAK1 to prevent its degradation in pancreatic cancer cells, contributing to gemcitabine resistance. USP33 mRNA stability is enhanced by METTL3 through m6A modification recognized by IGF2BP3. Co-immunoprecipitation, MeRIP-qPCR, RIP assay, USP33 knockdown with PAK1 ubiquitination and drug resistance readouts, xenograft model Naunyn-Schmiedeberg's archives of pharmacology Medium 41108357
2025 The zf-UBP and DUSP2 auxiliary domains of USP33 (and the homologous domains of USP20) are short linear motif (SLiM)-binding domains with similar binding profiles, explaining functional redundancy between USP33 and USP20. Consensus motifs recognized by these domains were defined. Proteomic-peptide phage display, peptide arrays, affinity measurements for SLiM-domain interactions bioRxivpreprint Medium bio_10.1101_2025.09.22.676098
2025 USP33 suppresses LATS1 ubiquitination (via Co-IP and CHX stability assay), thereby repressing the Hippo-YAP pathway, and localizes in autophagosomes to promote ferritinophagy and ferroptosis in endometriosis. Co-immunoprecipitation, cycloheximide chase assay, LATS1 ubiquitination assay, immunofluorescence co-localization with autophagosomes, ferroptosis markers (ROS, Fe2+, MDA, GSH) Gynecological endocrinology Low 41452077
2024 USP33 deubiquitinates and stabilizes EPHB2 in retinoblastoma cells, activating Wnt/β-catenin signaling; USP33 knockdown reduces EPHB2 protein and suppresses retinoblastoma growth in vitro and in vivo. Ubiquitination assay, protein stability assay, Co-immunoprecipitation, xenograft model Applied biochemistry and biotechnology Low 40824480

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. The EMBO journal 151 19424180
2009 Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2. Proceedings of the National Academy of Sciences of the United States of America 130 19363159
2019 USP33 deubiquitinates PRKN/parkin and antagonizes its role in mitophagy. Autophagy 112 31432739
2013 USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110. Nature 111 23486064
2009 Deubiquitinating enzyme USP33/VDU1 is required for Slit signaling in inhibiting breast cancer cell migration. Proceedings of the National Academy of Sciences of the United States of America 84 19706539
2013 The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune response. Nature cell biology 79 24056301
2021 SARS-CoV-2 Spike Targets USP33-IRF9 Axis via Exosomal miR-148a to Activate Human Microglia. Frontiers in immunology 75 33936086
2008 Human selenium binding protein-1 (hSP56) interacts with VDU1 in a selenium-dependent manner. Biochemical and biophysical research communications 69 19118533
2014 USP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migration. International journal of cancer 56 25242263
2019 Deubiquitinating enzyme USP33 restrains docetaxel-induced apoptosis via stabilising the phosphatase DUSP1 in prostate cancer. Cell death and differentiation 55 31857702
2009 Midline crossing and Slit responsiveness of commissural axons require USP33. Nature neuroscience 50 19684588
2019 Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2-Robo1 signalling on cell migration and EMT. Cell proliferation 46 30896071
2022 USP33 deubiquitinates and stabilizes HIF-2alpha to promote hypoxia response in glioma stem cells. The EMBO journal 41 35191554
2018 MicroRNA-365 promotes lung carcinogenesis by downregulating the USP33/SLIT2/ROBO1 signalling pathway. Cancer cell international 41 29743814
2014 USP33, a new player in lung cancer, mediates Slit-Robo signaling. Protein & cell 40 24981056
2020 Dengue Virus Degrades USP33-ATF3 Axis via Extracellular Vesicles to Activate Human Microglial Cells. Journal of immunology (Baltimore, Md. : 1950) 35 32848034
2021 Circular RNA circ_0057558 Controls Prostate Cancer Cell Proliferation Through Regulating miR-206/USP33/c-Myc Axis. Frontiers in cell and developmental biology 34 33718387
2007 The solution structure of the ZnF UBP domain of USP33/VDU1. Protein science : a publication of the Protein Society 34 17766394
2018 Radiation Enhances the Epithelial- Mesenchymal Transition of A549 Cells via miR3591-5p/USP33/PPM1A. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 33 30308513
2007 Expression patterns of WSB-1 and USP-33 underlie cell-specific posttranslational control of type 2 deiodinase in the rat brain. Endocrinology 31 17628004
2014 Degradation of the deubiquitinating enzyme USP33 is mediated by p97 and the ubiquitin ligase HERC2. The Journal of biological chemistry 29 24855649
2023 USP33 promotes pancreatic cancer malignant phenotype through the regulation of TGFBR2/TGFβ signaling pathway. Cell death & disease 27 37322017
2020 USP33 regulates c-Met expression by deubiquitinating SP1 to facilitate metastasis in hepatocellular carcinoma. Life sciences 25 32835698
2011 Isoform-specific localization of the deubiquitinase USP33 to the Golgi apparatus. Traffic (Copenhagen, Denmark) 24 21801292
2015 Specific CP110 Phosphorylation Sites Mediate Anaphase Catastrophe after CDK2 Inhibition: Evidence for Cooperation with USP33 Knockdown. Molecular cancer therapeutics 20 26304236
2022 Hepatokine ERAP1 Disturbs Skeletal Muscle Insulin Sensitivity Via Inhibiting USP33-Mediated ADRB2 Deubiquitination. Diabetes 17 35192681
2018 USP33 is a Biomarker of Disease Recurrence in Papillary Thyroid Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 15 29533940
2024 USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2. Oncogene 11 39256572
2023 Deubiquitinase USP33 promotes the glycolysis and growth of osteosarcoma by modifying PFKFB3 ubiquitination and degradation. American journal of cancer research 10 37034227
2023 USP33 enhances cell survival and stemness by deubiquitinating CTNNB1 in BXPC-3 and SW1990 cells. Cell biology international 9 37076992
2023 miR-206 alleviates LPS-induced inflammatory injury in cardiomyocytes via directly targeting USP33 to inhibit the JAK2/STAT3 signaling pathway. Molecular and cellular biochemistry 9 37256445
2023 USP33 promotes nonalcoholic fatty acid disease-associated fibrosis in gerbils via the c-myc signaling. Biochemical and biophysical research communications 8 37267862
2017 Deubiquitinase USP33 is negatively regulated by β-TrCP through ubiquitin-dependent proteolysis. Experimental cell research 7 28506875
2020 Downregulation of USP33 inhibits Slit/Robo signaling pathway and is associated with poor patient survival of glioma. Journal of neurosurgical sciences 6 32972109
2024 Ruthenium red alleviates post-resuscitation myocardial dysfunction by upregulating mitophagy through inhibition of USP33 in a cardiac arrest rat model. European journal of pharmacology 4 38703975
2024 USP33 Regulates DNA Damage Response and Carcinogenesis Through Deubiquitylating and Stabilising p53. Cell proliferation 3 39694539
2024 USP33 PROMOTES CERULEIN-INDUCED APOPTOTIC, OXIDATIVE, AND INFLAMMATORY INJURIES IN ACUTE PANCREATITIS BY DEUBIQUITINATING TRAF3. Shock (Augusta, Ga.) 2 39637362
2018 [USP33 suppresses lung adenocarcinoma lung cell invasion and metastasis by down-regulating SLIT2/ROBO1 signaling pathway]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2 30187867
2025 USP33-mediated stabilization of c-Myc drives glycolytic reprogramming and promotes ovarian cancer progression. Biochimica et biophysica acta. General subjects 1 40532745
2025 13-Docosenamide Enhances Oligodendrocyte Precursor Cell Differentiation via USP33-Mediated Deubiquitination of CNR1 in Chronic Cerebral Hypoperfusion. Neuroscience bulletin 1 40679549
2025 Synergistic inhibition of TNBC by USP33 and TAP63 through autophagy and ferroptosis activation. Cellular and molecular life sciences : CMLS 1 40801947
2024 RNA binding protein ELAVL1-mediated USP33 stabilizes HIF1A to promote pathological proliferation, migration and angiogenesis of RECs. International ophthalmology 1 39320536
2026 The role of deubiquitinase USP33 in colorectal cancer tumorigenesis and its potential as a therapeutic target predictor. Discover oncology 0 41661462
2026 USP33 contributes to EMT and Lenvatinib resistance by enhancing eEF1A1-mediated ILEI protein synthesis in hepatocellular carcinoma. International journal of biological macromolecules 0 42144151
2026 USP33 alleviates FIS1-dependent mitochondrial fission and cardiac microvascular injury in diabetic cardiomyopathy via deubiquitinating and stabilizing ATG7. Cell death & disease 0 42218158
2025 Phosphorylation of USP33 by CDK1 stabilizes the mTORC2 component SIN1. Cell death & disease 0 40695806
2025 USP33 Facilitates Retinoblastoma Growth by Deubiquitinating and Stabilizing EPHB2 Protein. Applied biochemistry and biotechnology 0 40824480
2025 METTL3/IGF2BP3 axis promotes gemcitabine resistance of pancreatic cancer cells through regulating USP33-mediated PAK1 deubiquitination and degradation. Naunyn-Schmiedeberg's archives of pharmacology 0 41108357
2025 Involvement of USP33 in ferritinophagy and ferroptosis in endometriosis through the Hippo-YAP pathway. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 0 41452077
2024 USP33 promotes pulmonary microvascular endothelial cell pyroptosis by stabilizing TRAF2 through deubiquitination. Histology and histopathology 0 39506557
2024 USP33 is an integrin α6 deubiquitinase and promotes esophageal squamous cell carcinoma cell migration and metastasis. Journal of cancer research and clinical oncology 0 39589547

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