Affinage

USP33

Ubiquitin carboxyl-terminal hydrolase 33 · UniProt Q8TEY7

Length
942 aa
Mass
106.7 kDa
Annotated
2026-04-28
49 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP33 is a cysteine deubiquitinase that stabilizes a broad array of substrates by removing K48-, K27-, K63-, K6-, and K11-linked ubiquitin chains, thereby controlling receptor trafficking, centrosome homeostasis, autophagy, mitophagy, and multiple signaling cascades. It deubiquitinates membrane receptors (β2AR, Robo1, TGFBR2, CNR1, integrin α6) to promote their recycling or surface retention and prevent lysosomal degradation, and it deubiquitinates signaling effectors (RALB at K47, CP110, Parkin at K435, HIF-2α, p53, c-Myc, β-catenin, SIN1, LATS1) to regulate their stability and pathway output (PMID:19424180, PMID:23486064, PMID:24056301, PMID:31432739, PMID:35191554, PMID:39694539, PMID:37322017, PMID:40695806). Substrate recruitment is mediated in part by SLiM-binding zf-UBP and DUSP2 auxiliary domains, and its catalytic activity is enhanced by CDK1-mediated phosphorylation [PMID:bio_10.1101_2025.09.22.676098, PMID:40695806]. USP33 itself is targeted for proteasomal destruction by the E3 ligases HERC2 (via p97/Ufd1-Npl4) and β-TrCP, and its mRNA is stabilized by METTL3-mediated m6A modification read by IGF2BP3 and by the RNA-binding protein ELAVL1, establishing multilayered control of USP33 abundance (PMID:24855649, PMID:28506875, PMID:41108357, PMID:39320536).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2007 High

    Solving the ZnF UBP domain structure revealed that, unlike USP5, USP33 coordinates three zinc ions and does not bind free ubiquitin through this domain, raising the question of how its auxiliary domains contribute to substrate selection.

    Evidence NMR spectroscopy of recombinant ZnF UBP domain

    PMID:17766394

    Open questions at the time
    • No substrate or functional role assigned to the ZnF UBP domain at this stage
    • Role of the three-zinc architecture unknown
  2. 2009 High

    Three contemporaneous studies established USP33 as a deubiquitinase controlling receptor trafficking: it deubiquitinates β2AR to promote receptor recycling from endosomes, deubiquitinates β-arrestin2 to modulate receptor–arrestin complex stability, and deubiquitinates/redistributes Robo1 to mediate Slit-dependent axon guidance and cancer cell migration inhibition.

    Evidence Co-IP, ubiquitination assays, receptor recycling/internalization assays in HEK293 cells; in vivo axon guidance assays in chick/mouse neural tube; migration assays in breast cancer cells

    PMID:19363159 PMID:19424180 PMID:19684588 PMID:19706539

    Open questions at the time
    • Structural basis for USP33 recognition of these diverse receptors unknown
    • Whether USP33 and USP20 are redundant for these substrates not resolved
  3. 2011 High

    Isoform mapping showed that alternative splicing generates USP33 variants with distinct subcellular localizations — all isoforms associate with ER, while one isoform additionally targets the Golgi — explaining how a single DUB can access substrates in different compartments.

    Evidence GFP-tagged isoform expression with immunofluorescence and deletion analysis in cultured cells

    PMID:21801292

    Open questions at the time
    • Which isoform acts on which substrate in vivo not determined
    • Regulation of isoform-specific splicing unknown
  4. 2013 High

    Two discoveries expanded USP33 function beyond receptor biology: it deubiquitinates CP110 at centrioles to control centrosome duplication, and it deubiquitinates RALB at K47 on starvation-induced vesicles to switch RALB from innate-immune to autophagy signaling.

    Evidence In vitro DUB assay for CP110, site-directed mutagenesis (K47) for RALB, centrosome duplication and autophagy assays

    PMID:23486064 PMID:24056301

    Open questions at the time
    • How USP33 is recruited to centrioles specifically in S/G2-M not resolved
    • Signal that triggers USP33 accumulation on RALB-positive vesicles during starvation not identified
  5. 2014 High

    The turnover of USP33 itself was shown to be controlled by HERC2-mediated polyubiquitination followed by p97/Ufd1-Npl4-dependent extraction and proteasomal degradation, establishing that USP33 abundance is tightly regulated at the post-translational level.

    Evidence Quantitative mass spectrometry, siRNA knockdown and chemical inhibition of p97, ubiquitination assays

    PMID:24855649

    Open questions at the time
    • Signal triggering HERC2-mediated USP33 degradation unknown
    • Whether HERC2 regulation is constitutive or stimulus-dependent not addressed
  6. 2017 Medium

    β-TrCP was identified as a second E3 ligase targeting USP33 for proteasomal degradation through an atypical interaction independent of the classical β-TrCP degron, indicating dual E3-mediated control of USP33 levels.

    Evidence Co-IP, domain mapping, ubiquitination assay with proteasome inhibitor

    PMID:28506875

    Open questions at the time
    • No phospho-degron identified; atypical binding mode not structurally resolved
    • Relative contributions of HERC2 vs. β-TrCP under different conditions unknown
  7. 2019 High

    USP33 was shown to localize to the outer mitochondrial membrane and to deubiquitinate Parkin at K435 (removing K6/K11/K48/K63 chains), thereby attenuating Parkin activation and suppressing mitophagy — extending USP33 function to mitochondrial quality control.

    Evidence In vitro and cellular DUB assays, K435 mutagenesis, mitophagy assays, mitochondrial fractionation

    PMID:31432739

    Open questions at the time
    • How USP33 OMM targeting is coordinated with mitochondrial depolarization not defined
    • Interplay with other Parkin-targeting DUBs (USP8, USP15, USP30) not addressed
  8. 2019 High

    USP33 was found to deubiquitinate DUSP1, preventing its K48-linked degradation and thereby suppressing JNK-mediated apoptosis in prostate cancer, revealing a role in stress-kinase signaling.

    Evidence Co-IP, K48-linkage-specific ubiquitination assay, JNK inhibitor epistasis in prostate cancer cells

    PMID:31857702

    Open questions at the time
    • Whether USP33-DUSP1 interaction is direct or scaffolded unknown
    • Broader relevance to other MAPK phosphatases not tested
  9. 2022 High

    Under hypoxia, ERK1/2 phosphorylates HIF-2α to enhance its binding to USP33, which deubiquitinates and stabilizes HIF-2α, driving glioma stem cell maintenance — demonstrating that signal-dependent substrate phosphorylation can regulate USP33 substrate engagement.

    Evidence Co-IP, ubiquitination assay, ERK inhibitor experiments, glioblastoma stem cell assays, in vivo tumor models

    PMID:35191554

    Open questions at the time
    • Phosphorylation site on HIF-2α mediating USP33 interaction not mapped
    • Whether USP33 similarly regulates HIF-1α stability under analogous conditions was only addressed separately (PMID:39320536)
  10. 2024 High

    Site-specific ubiquitinomics identified CBX2 K277 as a direct USP33 target where K27- and K48-linked chains are removed; GCN5-mediated acetylation of CBX2 at K199 enhances CBX2–USP33 interaction, establishing acetylation-deubiquitination crosstalk in substrate regulation.

    Evidence Proteomics, ubiquitinomics, site-directed mutagenesis (K277, K199), Co-IP

    PMID:39256572

    Open questions at the time
    • Structural basis for how K199 acetylation promotes USP33 binding not resolved
    • Whether this crosstalk operates for other USP33 substrates unknown
  11. 2024 High

    USP33 was shown to deubiquitinate p53 under DNA-damage conditions, and hepatocyte-specific USP33 knockout mice exhibited enhanced DEN-induced hepatocarcinogenesis, providing the first in vivo genetic evidence that USP33 functions as a tumor suppressor through p53 stabilization.

    Evidence Co-IP, ubiquitination assay, conditional knockout mouse model with chemical carcinogenesis

    PMID:39694539

    Open questions at the time
    • Whether USP33 competes with Mdm2 for p53 deubiquitination not established
    • Tissue-specific vs. general tumor-suppressive role of USP33 undefined
  12. 2025 High

    CDK1 was identified as a direct kinase activating USP33 via phosphorylation, with USP33 in turn deubiquitinating SIN1 to activate mTORC2–AKT signaling and drive pancreatic cancer chemoresistance, closing the loop on how cell-cycle kinase signaling modulates USP33 catalytic output.

    Evidence CDK1 kinase assay, Co-IP, ubiquitination assay, genetic ablation of CDK1/USP33/SIN1, in vivo tumor models

    PMID:40695806

    Open questions at the time
    • Phosphorylation sites on USP33 not mapped
    • Whether CDK1-USP33 regulation extends to other G2/M substrates (e.g. CP110) not tested
  13. 2025 Medium

    Proteomic peptide phage display showed that the zf-UBP and DUSP2 domains of USP33 function as SLiM-binding modules with binding profiles overlapping USP20, providing a structural rationale for broad substrate recognition and functional redundancy between these paralogous DUBs.

    Evidence Proteomic-peptide phage display, peptide arrays, affinity measurements (preprint)

    PMID:bio_10.1101_2025.09.22.676098

    Open questions at the time
    • Preprint; awaits peer review
    • Which specific SLiMs in individual substrates are recognized not mapped
    • In vivo validation of SLiM-dependent substrate recruitment not performed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the full catalytic-domain structure of USP33, the phosphorylation sites through which CDK1 activates it, the degree of functional redundancy with USP20 in vivo, how isoform-specific splicing is regulated to direct compartment-specific substrate access, and whether USP33 has genuine substrate selectivity rules or acts broadly on accessible ubiquitinated proteins in its vicinity.
  • No full-length catalytic domain crystal/cryo-EM structure
  • CDK1 phosphorylation sites on USP33 unmapped
  • No genetic study comparing USP33/USP20 double knockout
  • Substrate specificity rules beyond SLiM-binding domains not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016787 hydrolase activity 6
Localization
GO:0005739 mitochondrion 1 GO:0005768 endosome 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 9 R-HSA-392499 Metabolism of proteins 6 R-HSA-168256 Immune System 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2 R-HSA-1266738 Developmental Biology 1 R-HSA-1640170 Cell Cycle 1
Partners
ADRB2ARRB2CP110EPAS1PRKNRALBROBO1TP53

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 USP33 constitutively binds beta2-adrenergic receptor (β2AR) and dissociates immediately after agonist stimulation, then reassociates on prolonged agonist treatment; USP33 deubiquitinates β2AR to inhibit lysosomal trafficking and promote receptor recycling from late-endosomal compartments, thereby resensitizing receptors at the cell surface. Co-immunoprecipitation, ubiquitination assays, receptor trafficking/recycling assays in HEK293 cells, fluorescence microscopy The EMBO journal High 19424180
2009 USP33 binds beta-arrestin2 and deubiquitinates it, opposing Mdm2-mediated ubiquitination; this reciprocal regulation controls the stability of the receptor–beta-arrestin complex, subcellular localization of receptor signalosomes, and β2AR internalization. Class A receptors (e.g., β2AR) promote a beta-arrestin conformation that favors USP33 binding, whereas class B receptors (e.g., V2R) favor USP33 dissociation. Co-immunoprecipitation, in vivo ubiquitination assay, receptor internalization assay, siRNA knockdown, confocal microscopy Proceedings of the National Academy of Sciences of the United States of America High 19363159
2009 USP33 binds Robo1 receptor and is required for Slit-induced redistribution of Robo1 from intracellular compartments to the plasma membrane, and for Slit-mediated inhibition of directional breast cancer cell migration. Co-immunoprecipitation, siRNA knockdown, cell migration assays, receptor localization by fluorescence microscopy Proceedings of the National Academy of Sciences of the United States of America High 19706539
2009 USP33 is required for Slit-mediated axon guidance at the ventral midline; it interacts with Robo1 and is essential for commissural axon midline crossing in vertebrates. Co-immunoprecipitation, in vivo knockdown in chick/mouse neural tube, axon guidance assays Nature neuroscience High 19684588
2007 The ZnF UBP domain of USP33/VDU1 was solved by NMR spectroscopy; the structure contains three zinc ions (unlike the single Zn of USP5) and, unlike the USP5 ZnF UBP domain, does not bind ubiquitin. NMR spectroscopy, structural determination Protein science High 17766394
2013 USP33 localizes to centrioles primarily in S and G2/M phases, interacts with CP110, and potently and specifically deubiquitinates CP110 (but not other cyclin-F substrates), thereby antagonizing SCF(cyclin F)-mediated ubiquitination and promoting supernumerary centriole generation; USP33 ablation destabilizes CP110 and inhibits centrosome amplification. Co-immunoprecipitation, in vivo and in vitro ubiquitination assays, centrosome duplication assays, siRNA knockdown, immunofluorescence localization Nature High 23486064
2013 Nutrient starvation induces USP33 accumulation and relocalization to RALB-positive vesicles, where USP33 deubiquitylates RALB at Lys47; deubiquitylated RALB preferentially interacts with EXO84 to drive autophagosome formation, while ubiquitylated RALB favors SEC5-TBK1 innate immune signaling. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K47), autophagy assays, confocal microscopy Nature cell biology High 24056301
2014 USP33 is degraded via the ubiquitin-proteasome system; HERC2 (a HECT-domain E3 ligase) polyubiquitinates USP33, and p97 (with its Ufd1-Npl4 adaptor complex) is required for post-ubiquitination processing and degradation of USP33. Quantitative mass spectrometry, siRNA knockdown of p97/HERC2, chemical inhibition of p97, ubiquitination assays The Journal of biological chemistry High 24855649
2014 USP33 deubiquitinates and stabilizes Robo1 in lung cancer cells, mediating Slit-Robo signaling to inhibit lung cancer cell migration. siRNA knockdown, Co-immunoprecipitation, ubiquitination assay, cell migration assay Protein & cell Medium 24981056
2014 USP33 deubiquitinates and stabilizes Robo1 in colorectal cancer cells, required for Slit2-mediated inhibition of CRC cell migration. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, cell migration assay International journal of cancer Medium 25242263
2011 USP33 exists as multiple splice variants with isoform-specific subcellular localization: all variants localize to ER-associated structures, while variant 3 additionally accumulates at the Golgi; two distinct inserts in the catalytic domain mediate ER association and membrane association respectively, and alternative splicing of eight amino acids in insert 2 enables Golgi targeting. GFP-tagged isoform expression, immunofluorescence microscopy, fractionation, deletion/splice variant analysis Traffic High 21801292
2019 USP33 localizes to the outer mitochondrial membrane, binds PRKN/parkin, and deubiquitinates PRKN in a DUB activity-dependent manner; USP33 preferentially removes K6, K11, K48, and K63-linked ubiquitin chains from PRKN, primarily at Lys435 (K63-linked chains); USP33 knockdown enhances both PRKN stabilization and its translocation to depolarized mitochondria, thereby increasing mitophagy. Co-immunoprecipitation, in vitro and cellular ubiquitination assays, site-directed mutagenesis (K435), mitophagy assays, mitochondrial fractionation Autophagy High 31432739
2019 USP33 interacts with DUSP1 phosphatase and inhibits its K48-linked polyubiquitination and proteasomal degradation; USP33 knockdown promotes DUSP1 degradation leading to enhanced JNK activation and docetaxel-induced apoptosis in prostate cancer cells. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown/KO, JNK inhibitor rescue experiments Cell death and differentiation High 31857702
2017 The E3 ligase β-TrCP interacts with USP33 (via WD40 motif of β-TrCP and the 201-400 aa region of USP33, independently of the classic β-TrCP binding motif) and mediates USP33 ubiquitination and proteasomal degradation. Co-immunoprecipitation, deletion mapping, ubiquitination assay, proteasome inhibitor treatment Experimental cell research Medium 28506875
2021 USP33 deubiquitylates IRF9 to regulate its stability; SARS-CoV-2 Spike-induced exosomal miR-148a suppresses USP33 expression in human microglia, leading to decreased IRF9 levels and hyperactivation of pro-inflammatory TNFα, NF-κB, and IFN-β pathways. miRNA overexpression/knockdown, luciferase reporter assay, immunoblotting, in vivo ubiquitination assay Frontiers in immunology Medium 33936086
2020 USP33 deubiquitylates ATF3 to stabilize it; DENV-NS1-induced exosomal miR-148a suppresses USP33 in human microglia, reducing ATF3 stability and disinhibiting TNF-α, NF-κB, and IFN-β pro-inflammatory signaling. EV cargo analysis, miRNA mimic/anti-miR, dual luciferase reporter, in vivo ubiquitination assay, chase assay Journal of immunology Medium 32848034
2022 USP33 is preferentially induced in glioma stem cells by hypoxia, interacts with HIF-2α, and deubiquitinates and stabilizes HIF-2α protein; ERK1/2 activation upon hypoxia promotes HIF-2α phosphorylation, enhancing its interaction with USP33. USP33 silencing disrupts glioma stem cell maintenance and reduces tumor vascularization. Co-immunoprecipitation, ubiquitination assay, ERK inhibitor experiments, siRNA knockdown, glioblastoma stem cell maintenance assays, in vivo tumor models The EMBO journal High 35191554
2022 ERAP1 hepatokine interacts with β2 adrenergic receptor (ADRB2) and reduces its expression by decreasing USP33-mediated deubiquitination of ADRB2, thereby disrupting ADRB2-stimulated insulin signaling in skeletal muscle. Co-immunoprecipitation, ubiquitination assay, hepatic overexpression/knockdown in mice, insulin signaling assays Diabetes Medium 35192681
2018 USP33 deubiquitinates PPM1A (a Smad2/3 phosphatase); miR-3591-5p targets USP33 to reduce PPM1A stability, thereby activating TGF-β/Smad2/3 signaling and promoting radiation-induced EMT in lung cancer cells. Luciferase reporter assay (3'UTR), ubiquitination assay, ectopic expression rescue, Western blot Cellular physiology and biochemistry Medium 30308513
2023 USP33 interacts with TGFBR2 (TGF-β receptor 2), deubiquitinates it, and prevents its lysosomal degradation, promoting TGFBR2 accumulation at the cell membrane and sustained TGF-β signaling; TGF-β target ZEB1 in turn transcriptionally activates USP33 forming a positive feedback loop. Mass spectrometry, luciferase complementation assay, Co-immunoprecipitation, ubiquitination assay, lysosome inhibition experiments Cell death & disease Medium 37322017
2020 USP33 directly binds SP1 transcription factor and deubiquitinates it, stabilizing SP1 protein and upregulating c-Met expression, thereby promoting hepatocellular carcinoma invasion and metastasis. Co-immunoprecipitation, ubiquitination assay, RNA sequencing, luciferase reporter, in vivo metastasis model Life sciences Medium 32835698
2021 USP33 interacts with and deubiquitinates c-Myc; circ_0057558 sponges miR-206 to increase USP33 expression, which stabilizes c-Myc and promotes prostate cancer cell proliferation. RNA pulldown, luciferase assay, Co-immunoprecipitation, ubiquitination assay Frontiers in cell and developmental biology Medium 33718387
2023 USP33 deubiquitinates JAK2 to activate JAK2/STAT3 signaling in cardiomyocytes; miR-206 targets USP33 to suppress this pathway and protect against LPS-induced inflammatory injury. Co-immunoprecipitation, ubiquitination assay, dual luciferase reporter, siRNA knockdown rescue experiments Molecular and cellular biochemistry Medium 37256445
2023 USP33 interacts with CTNNB1 (β-catenin) and deubiquitinates it, preventing its degradation and promoting pancreatic cancer cell proliferation and self-renewal. Co-immunoprecipitation, ubiquitination assay, sphere formation, colony formation assays Cell biology international Medium 37076992
2023 USP33 stabilizes PFKFB3 by suppressing its ubiquitin-mediated degradation, driving aerobic glycolysis and osteosarcoma cell growth. Co-immunoprecipitation, ubiquitination assay, glycolysis functional assays American journal of cancer research Low 37034227
2024 USP33 removes K27- and K48-linked ubiquitin chains from CBX2 at K277; acetylation of CBX2 at K199 by acetyltransferase GCN5 enhances CBX2 interaction with USP33, promoting further deubiquitination and stabilization of CBX2 to drive ovarian cancer progression. Proteomics, ubiquitinomics, Co-immunoprecipitation, site-directed mutagenesis (K277, K199), ubiquitination assay Oncogene High 39256572
2024 USP33 interacts with and deubiquitinates p53 to stabilize it under DNA damage conditions; USP33 depletion increases p53 ubiquitination and impairs DNA damage-induced cell cycle arrest and apoptosis; hepatocyte-specific USP33 knockout mice show enhanced sensitivity to DEN-induced hepatocarcinogenesis. Co-immunoprecipitation, in vivo ubiquitination assay, USP33 knockout mouse model, liver carcinogenesis assay Cell proliferation High 39694539
2024 USP33 interacts with TRAF3, deubiquitinates it, and upregulates its expression, activating the NF-κB pathway to promote apoptosis, oxidative stress, and inflammation in cerulein-induced acute pancreatitis. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, immunofluorescence, NF-κB pathway assays Shock Medium 39637362
2024 USP33 mediates cell migration in esophageal squamous cell carcinoma by binding, deubiquitinating, and stabilizing integrin α6; USP33 knockdown inhibits laminin-dependent adhesion, spreading, migration, and metastasis. Co-immunoprecipitation, deubiquitination assay, cell adhesion/migration/spreading assays, tail vein injection metastasis model Journal of cancer research and clinical oncology Medium 39589547
2024 USP33 stabilizes TRAF2 by deubiquitination, promoting pyroptosis of human pulmonary microvascular endothelial cells during hypoxia/reoxygenation-induced acute lung injury. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, pyroptosis markers assay Histology and histopathology Low 39506557
2024 USP33 stabilizes CNR1 (cannabinoid receptor 1) via deubiquitination in oligodendrocyte precursor cells, activating AKT/mTOR signaling to promote OPC differentiation; 13-docosenamide upregulates this USP33-mediated CNR1 deubiquitination. Co-immunoprecipitation, ubiquitination assay, in vivo BCAS mouse model, AKT/mTOR signaling assays Neuroscience bulletin Medium 40679549
2025 CDK1 directly phosphorylates USP33, enhancing its deubiquitinase activity toward SIN1 (mTORC2 component); USP33 deubiquitinates and stabilizes SIN1 to activate the mTORC2-AKT pathway, driving chemoresistance in pancreatic cancer. Co-immunoprecipitation, ubiquitination assay, CDK1 kinase assay, genetic ablation of CDK1/USP33/SIN1, in vivo tumor models Cell death & disease High 40695806
2025 USP33 deubiquitinates PAK1 to prevent its degradation; METTL3-mediated m6A modification of USP33 mRNA, read by IGF2BP3, stabilizes USP33 transcript and increases USP33 protein, promoting gemcitabine resistance in pancreatic cancer. Co-immunoprecipitation, MeRIP-qPCR, RIP assay, ubiquitination assay, xenograft model Naunyn-Schmiedeberg's archives of pharmacology Medium 41108357
2025 USP33 stabilizes TAP63 through K48-linked deubiquitination, triggering autophagy and ferroptosis in triple-negative breast cancer by disrupting mitochondrial function and redox balance. Co-immunoprecipitation, ubiquitin chain analysis (K48), ferroptosis/autophagy markers, in vivo xenograft Cellular and molecular life sciences Medium 40801947
2025 USP33 deubiquitinates c-Myc at K48-linked chains to stabilize it, enhancing c-Myc transcriptional activity and driving glycolytic reprogramming (upregulating LDHA, GLUT1, PKM2) in ovarian cancer. Co-immunoprecipitation, ubiquitination assay (K48-specific), c-Myc overexpression rescue, metabolic assays Biochimica et biophysica acta. General subjects Medium 40532745
2025 USP33 suppresses LATS1 ubiquitination to inhibit the Hippo-YAP pathway, thereby promoting ferritinophagy and ferroptosis in endometrial stromal cells; USP33 is also localized in autophagosomes and promotes ferritin degradation therein. Co-immunoprecipitation, ubiquitination assay, CHX chase assay, ROS/Fe2+/MDA measurements, immunofluorescence colocalization Gynecological endocrinology Medium 41452077
2025 USP33 deubiquitinates and stabilizes EPHB2, activating Wnt/β-catenin signaling to promote retinoblastoma cell proliferation, invasion, and stemness. Co-immunoprecipitation, ubiquitination assay, protein stability assay, xenograft mouse model Applied biochemistry and biotechnology Low 40824480
2025 The zf-UBP and DUSP2 auxiliary domains of USP33 are short linear motif (SLiM)-binding domains with binding profiles similar to those of USP20, explaining functional redundancy between the two DUBs; these domains mediate substrate targeting via SLiMs in intrinsically disordered regions. Proteomic-peptide phage display, peptide arrays, affinity measurements bioRxivpreprint Medium bio_10.1101_2025.09.22.676098
2008 USP33/VDU1 interacts with human selenium-binding protein-1 (hSP56) in a selenium-dependent manner, with full-length VDU1 specifically binding the selenium-replete form of hSP56; the two proteins co-localize in the perinuclear region of prostate cancer cells. Yeast two-hybrid, in vitro binding assay, co-localization by immunofluorescence Biochemical and biophysical research communications Low 19118533
2024 USP33 deubiquitinates HIF1A (HIF-1α) to stabilize it in hypoxia-exposed human retinal vascular endothelial cells; the RNA-binding protein ELAVL1 stabilizes USP33 mRNA to maintain USP33 protein levels and sustain HIF1A stability. Immunoprecipitation, ubiquitination assay, RNA immunoprecipitation (RIP), actinomycin D stability assay International ophthalmology Medium 39320536

Source papers

Stage 0 corpus · 49 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
2013 USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110. Nature 111 23486064
2019 USP33 deubiquitinates PRKN/parkin and antagonizes its role in mitophagy. Autophagy 108 31432739
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 78 24056301
2021 SARS-CoV-2 Spike Targets USP33-IRF9 Axis via Exosomal miR-148a to Activate Human Microglia. Frontiers in immunology 73 33936086
2008 Human selenium binding protein-1 (hSP56) interacts with VDU1 in a selenium-dependent manner. Biochemical and biophysical research communications 68 19118533
2014 USP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migration. International journal of cancer 55 25242263
2019 Deubiquitinating enzyme USP33 restrains docetaxel-induced apoptosis via stabilising the phosphatase DUSP1 in prostate cancer. Cell death and differentiation 53 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 44 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
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 The solution structure of the ZnF UBP domain of USP33/VDU1. Protein science : a publication of the Protein Society 33 17766394
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 10 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 8 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 2 39694539
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
2024 USP33 PROMOTES CERULEIN-INDUCED APOPTOTIC, OXIDATIVE, AND INFLAMMATORY INJURIES IN ACUTE PANCREATITIS BY DEUBIQUITINATING TRAF3. Shock (Augusta, Ga.) 1 39637362
2026 The role of deubiquitinase USP33 in colorectal cancer tumorigenesis and its potential as a therapeutic target predictor. Discover oncology 0 41661462
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