| 2009 |
USP36 localizes to nucleoli via a C-terminal basic amino acid region and deubiquitinates nucleolar proteins nucleophosmin/B23 and fibrillarin, stabilizing them against ubiquitylation-mediated proteasomal degradation. RNAi-mediated depletion reduces rRNA transcription and processing, nucleolar morphology, and cell proliferation. |
Dominant-negative inhibition, RNAi knockdown, co-immunoprecipitation, in vitro deubiquitylation assay, subcellular fractionation/imaging |
Journal of cell science |
High |
19208757
|
| 2009 |
Nucleophosmin/B23 recruits USP36 to nucleoli by interacting with a specific basic amino acid motif (RGKEKKIKKFKREKRR) in USP36's C-terminal region. Knockdown of nucleophosmin/B23 reduces nucleolar USP36 levels and elevates fibrillarin ubiquitylation. |
Nucleolar localization signal mapping, Co-IP, RNAi knockdown, ubiquitylation assay |
The Journal of biological chemistry |
High |
19679658
|
| 2005 |
USP36 possesses deubiquitinase activity (cleaves ubiquitin from substrates), contains a PEST motif, and is itself polyubiquitinated. |
RT-PCR cloning, ubiquitin-cleavage activity assay, immunoprecipitation, structural domain analysis |
Biochemical and biophysical research communications |
Medium |
15809067
|
| 2011 |
USP36 interacts with mitochondrial antioxidant enzyme SOD2, reduces its polyubiquitination, and stabilizes it against proteasomal degradation, extending its half-life. |
2D-gel electrophoresis, MALDI-TOF/MS identification, co-immunoprecipitation, yeast two-hybrid, ubiquitination assay |
Journal of cellular biochemistry |
Medium |
21268071
|
| 2012 |
USP36 (dUsp36) loss of function in Drosophila and human cells activates p62/SQSTM1-dependent selective autophagy of ubiquitinated cargo; dUSP36 loss leads to nuclear accumulation of ubiquitinated proteins (including histone H2B) and cytoplasmic ubiquitinated aggregates eliminated by autophagy. dUSP36 is not part of the TOR signaling pathway. |
Drosophila loss-of-function genetics, RNAi in human cells, p62/SQSTM1 requirement epistasis, fluorescence imaging of ubiquitin aggregates |
Autophagy |
High |
22622177
|
| 2015 |
USP36 is a nucleolar deubiquitinase for c-Myc: it interacts with and deubiquitinates c-Myc in cells and in vitro, stabilizing it against SCF(Fbw7)-mediated degradation in the nucleolus. USP36 interacts with nucleolar Fbw7γ but not nucleoplasmic Fbw7α, yet abolishes c-Myc degradation by both. USP36 is also a c-Myc target gene, forming a positive feedback loop. |
Co-immunoprecipitation, in vitro deubiquitination assay, knockdown, c-Myc stability assay, isoform-specific interaction mapping |
Proceedings of the National Academy of Sciences of the United States of America |
High |
25775507
|
| 2016 |
USP36 binds Nedd4-2 and regulates its association with TrkA neurotrophin receptor indirectly (USP36 does not directly deubiquitinate TrkA). Depletion of USP36 increases TrkA–Nedd4-2 complex formation, enhancing TrkA ubiquitination; USP36 overexpression disrupts this complex. USP36 also interferes with Nedd4-2-dependent regulation of Kv7.2/3 channels. |
siRNA screen, Co-IP, overexpression/depletion, TrkA ubiquitination assay, PC12 differentiation assay |
The Journal of biological chemistry |
Medium |
27445338
|
| 2017 |
USP36 deubiquitinates and stabilizes the DEAH-box RNA helicase DHX33 in the nucleolus. Usp36 knockout in mice is lethal at the morula-to-blastocyst transition. USP36 depletion impairs rRNA synthesis, protein translation, cell proliferation, and induces apoptosis and cell cycle arrest in human cancer cells. |
Usp36 knockout mouse model, electron microscopy, Northern blot, O-propargyl-puromycin protein synthesis assay, ubiquitination assay, Co-IP |
The Journal of biological chemistry |
High |
29273634
|
| 2017 |
USP36 is a histone H2B deubiquitinase: it interacts with H2B and deubiquitinates monoubiquitinated H2B (H2Bub1) in cells and in vitro. USP36 depletion increases H2Bub1 at the p21 locus gene body, inducing p21 expression and inhibiting cell proliferation. |
Co-IP, in vitro deubiquitination assay, overexpression, knockdown, ChIP at p21 locus |
Biochemical and biophysical research communications |
Medium |
29274341
|
| 2018 |
USP36 controls cellular localization of CHD7; in neuroblastoma, lncRNAs CASC15/NBAT1 modulate USP36 localization, which in turn regulates CHD7 stability and downstream SOX9 expression. |
Loss-of-function experiments, co-immunoprecipitation, immunoblotting, localization studies |
Cancer cell |
Medium |
29533783
|
| 2018 |
USP36 deubiquitinates and stabilizes PME-1 (protein phosphatase methylesterase 1), thereby promoting ERK and Akt signaling pathways. |
Co-IP, USP36 knockdown/overexpression, ubiquitination assay, western blot for ERK/Akt activation |
FEBS letters |
Medium |
29577269
|
| 2019 |
USP36 knockdown impairs Parkin-dependent mitophagy by reducing mRNA and protein levels of Beclin-1 and ATG14L (without altering nucleolar USP36 localization during mitophagy); restoration of ATG14L rescues mitophagy in USP36-silenced cells. |
High-content imaging siRNA screen, knockdown, immunofluorescence, western blot, ATG14L overexpression rescue |
Experimental cell research |
Medium |
31550441
|
| 2020 |
USP36 interacts with PrimPol, deubiquitinates K29-linked polyubiquitin chains on PrimPol, and increases PrimPol protein stability in response to DNA replication stress. USP36 is itself deubiquitinated following replication stress, facilitating its upregulation. |
Co-IP, mass spectrometry, in vivo and in vitro ubiquitination assays, replication stress assays, cisplatin/olaparib sensitivity |
Nucleic acids research |
High |
33237263
|
| 2021 |
USP36 promotes nucleolar SUMOylation: it interacts with SUMO2 and Ubc9, directly mediates SUMOylation in cells and in vitro, and specifically SUMOylates snoRNP components Nop58, Nhp2, Nop56, and DKC1, promoting their binding to snoRNAs. USP36 knockdown markedly impairs rRNA processing and translation. |
Overexpression, knockdown, genetic deletion, Co-IP, in vitro SUMOylation assay, snoRNA binding assay, rRNA processing assay |
EMBO reports |
High |
33852194
|
| 2021 |
USP36 cleaves the ribosomal fusion protein FUBI-eS30: purified USP36 cuts FUBI-eS30 in vitro, and USP36 depletion by RNAi or CRISPRi impairs FUBI-eS30 processing and late steps of cytoplasmic 40S maturation including 18S rRNA maturation and recycling of biogenesis factors. |
Differential affinity purification, RNAi, CRISPRi, in vitro processing assay with purified USP36, rRNA processing analysis |
eLife |
High |
34318747
|
| 2021 |
USP36 deubiquitinates and stabilizes DOCK4 (a guanine nucleotide exchange factor); increased USP36-DOCK4 stabilization activates Wnt/β-catenin signaling and promotes epithelial-to-mesenchymal transition in diabetic renal tubular epithelial cells. |
Co-IP, deubiquitination assay, knockdown/overexpression, Wnt pathway reporter |
Frontiers in cell and developmental biology |
Medium |
33968925
|
| 2022 |
USP36 deubiquitinates and stabilizes YAP by blocking K48-linked polyubiquitination, thereby promoting Hippo/YAP signaling in esophageal squamous carcinoma. |
siRNA DUB screening, Co-IP, ubiquitination assay, knockdown/overexpression, western blot |
Cell death & disease |
Medium |
36470870
|
| 2022 |
USP36 activates Snail2 deubiquitination in glioblastoma, downstream of PRL1 oncogene; PRL1 promotes EMT and invasion by activating USP36-mediated Snail2 stabilization. |
Co-IP, ubiquitination assay, knockdown/overexpression, in vitro and in vivo tumorigenesis assays |
Frontiers in oncology |
Medium |
35111679
|
| 2023 |
USP36 interacts with EXOSC10 (nucleolar RNA exosome subunit) and mediates its SUMOylation at K583. K583 SUMOylation is required for EXOSC10 binding to pre-rRNAs; K583R mutant fails to rescue rRNA processing and cell growth defects upon EXOSC10 knockdown. USP36 does not significantly regulate EXOSC10 protein levels. |
Co-IP, in vitro SUMOylation assay, mutant rescue, rRNA processing assay, RNA binding assay |
Nucleic acids research |
High |
36912080
|
| 2023 |
USP36 deubiquitinates and stabilizes ALKBH5, regulating ALKBH5-mediated gene expression in glioblastoma. Depletion of USP36 impairs glioma stem cell self-renewal, proliferation, and sensitizes cells to temozolomide. |
DUB siRNA library screen, mass spectrometry, Co-IP, in vivo and in vitro ubiquitination assays, neurosphere formation, intracranial tumor growth |
Neuro-oncology |
High |
36239338
|
| 2023 |
Crystal structures of USP36 in complex with ubiquitin and Fubi reveal the substrate recognition mechanism for dual ubiquitin/Fubi cleavage activity. USP16 was also identified as having dual ubiquitin/Fubi cleavage activity by chemoproteomics; both USP16 and USP36 participate in Fubi-S30 maturation. |
Crystal structure determination, chemoproteomics, Fubi C-terminal hydrolase activity assay, substrate specificity analysis |
Nature chemical biology |
High |
37443395
|
| 2023 |
Ribotoxic stress activates JNK, which in turn activates USP36, leading to stabilization of Snail1 in the nucleolus. Nucleolar Snail1 facilitates ribosome biogenesis and tumor cell survival, and mediates solid tumor resistance to homoharringtonine (HHT). |
Co-IP, knockdown, JNK inhibition, HHT treatment, ribosome biogenesis assay, combination therapy in vivo |
Nature communications |
Medium |
37833415
|
| 2023 |
USP36 associates with the Drosha-DGCR8 microprocessor complex and mediates DGCR8 SUMOylation by SUMO2. This SUMOylation promotes DGCR8 binding to pri-miRNAs without affecting DGCR8 levels or the Drosha-DGCR8 complex. USP36 knockdown attenuates pri-miRNA processing and reduces mature miRNA levels. |
Co-IP, in vitro/in vivo SUMOylation assay, SUMO site mapping, RNA immunoprecipitation, knockdown, cell proliferation assay |
Cancer research communications |
High |
36950067
|
| 2024 |
USP36 binds PARP1 and mediates its deubiquitination, increasing PARP1 protein stability in cardiomyocytes exposed to doxorubicin. The catalytically inactive C131A mutant of USP36 fails to stabilize PARP1, confirming catalytic dependence. Cardiac knockdown of USP36 (rAAV9-shUSP36) preserved cardiac function in a doxorubicin-induced cardiomyopathy mouse model. |
Co-IP, ubiquitination assay, catalytic mutant (C131A), rAAV9 in vivo knockdown, cardiac function assessment |
Cellular signalling |
High |
38307305
|
| 2024 |
USP36 deubiquitinates survivin (removing K48-linked chains) and cIAP1 (removing K11-linked chains), stabilizing both anti-apoptotic proteins. USP36 disrupts XIAP-SMAC complex formation and promotes RIP1 ubiquitination, thereby inhibiting both intrinsic and extrinsic apoptosis in colorectal cancer cells. |
siRNA gene silencing, Co-IP, ubiquitin linkage-specific assays, apoptosis assays |
The Journal of biological chemistry |
Medium |
38876304
|
| 2024 |
USP36 deubiquitinates ERα, inhibiting K48-linked polyubiquitination and stabilizing ERα protein; the catalytically inactive C131A mutant fails to promote breast cancer progression through ERα signaling. USP36 knockdown destabilizes the tamoxifen-resistant ERα mutant (Y537S). |
DUB siRNA library screen, Co-IP, ubiquitination assay, catalytic mutant (C131A), xenograft model, RNA sequencing |
Journal of experimental & clinical cancer research : CR |
High |
39215346
|
| 2024 |
USP36 deubiquitinates and stabilizes RBM28 at K162; upregulated RBM28 binds p53 and suppresses its transcriptional activity, inactivating the p53 signaling pathway in colorectal cancer. |
Co-IP, ubiquitination assay (site-specific K162), knockdown/overexpression, p53 transcription reporter |
Oncogene |
Medium |
39343961
|
| 2024 |
USP36 SUMOylates Las1L at K565; K565 SUMOylation is essential for ITS2 pre-rRNA processing but not for Las1L protein levels or Las1L-Nol9 complex formation. USP36 also deubiquitinates Las1L and Nol9, regulating their stability. |
Co-IP, in vitro SUMOylation assay, K565R mutant rescue, ITS2 processing assay, ubiquitination assay |
Cancer research communications |
High |
39356143
|
| 2024 |
USP36 interacts with WDR5 and stabilizes it via deubiquitination; USP36 knockdown increases WDR5 ubiquitination and degradation, impairing osteogenic differentiation. Overexpression of WDR5 rescues the differentiation defects in USP36-deficient osteoblasts. |
Co-IP, ubiquitination assay, knockdown, Alizarin red staining, WDR5 rescue overexpression |
Journal of orthopaedic surgery and research |
Medium |
39152465
|
| 2024 |
A germline USP36 variant (rs3744797, K814N) stabilizes MLLT3 via deubiquitination in the nucleolus, activating HIF1α and Snai downstream signaling and conferring resistance to EGFR-TKIs in non-small cell lung cancer. |
m6A-genome-wide-variant analysis, Co-IP, ubiquitination assay, in vitro/in vivo functional assays, patient cohort |
Clinical cancer research : an official journal of the American Association for Cancer Research |
Medium |
38261467
|
| 2025 |
MMA (methylmalonic acid) induces methylmalonylation of USP36 at K499, inhibiting USP36-mediated deubiquitination and SUMOylation of SUFU, thereby promoting GLI1 expression and Hedgehog pathway activation in clear-cell renal cell carcinoma macrophages. |
Metabolomic profiling, site-specific modification analysis, ubiquitination and SUMOylation assays, in vitro and in vivo functional experiments |
Cell death and differentiation |
Medium |
41398045
|
| 2025 |
In Drosophila, catalytically inactive dUSP36 (CRISPR knock-in) allows survival to adulthood with minor growth defects, demonstrating that the deubiquitinating activity is dispensable for cell growth but essential for spermatogenesis, revealing both catalytic-dependent and catalytic-independent mechanisms. |
CRISPR/Cas9 catalytic mutation knock-in, null mutant comparison, viability and fertility assays |
Genetics |
High |
40646716
|
| 2025 |
USP36 stabilizes APEX1 by removing K48-linked ubiquitin chains, suppressing ferroptosis in melanoma cells. USP36 knockdown sensitizes xenograft tumors to ferroptosis, and APEX1 knockdown abolishes USP36's anti-ferroptotic effect. |
Co-IP, ubiquitination assay (K48-specific), overexpression/knockdown, erastin treatment, xenograft model |
Clinical and experimental medicine |
Medium |
41649582
|
| 2025 |
USP36 functions as a SUMO ligase for GNL3 (nucleolar GTP-binding protein), while SENP3 deSUMOylates GNL3. GNL3 SUMOylation is required for interaction with the BLM-DNA2 complex and DNA end resection in homologous recombination repair. |
Co-IP, in vitro SUMOylation assay, CRISPR/RNAi knockdown, DNA end resection assay, epistasis with SENP3 |
bioRxivpreprint |
Medium |
|
| 2025 |
USP36 stabilizes KIF2C by removing K48-linked ubiquitin chains, suppressing ferroptosis in breast cancer cells. USP36-deficient xenograft tumors show reduced proliferation and increased ferroptosis. |
Co-IP, K48-specific ubiquitination assay, knockdown/overexpression, erastin ferroptosis assay, xenograft model |
Biochemical pharmacology |
Medium |
40744233
|
| 2025 |
USP36 deubiquitinates and stabilizes AR (androgen receptor) in prostate cancer cells under oxidative stress (H2O2); USP36–AR interaction is induced by H2O2 and knockdown of USP36 abolishes H2O2-induced activation of the AR-PSA pathway. |
TurboID proximity labeling plus mass spectrometry, Co-IP, ubiquitination assay, dual-luciferase reporter, knockdown |
Scientific reports |
Medium |
41298501
|
| 2025 |
FBL (fibrillarin) acts as a carrier regulating the balance between BMI1-mediated H2A monoubiquitination and USP36-mediated H2Aub deubiquitination in nucleolar lysosome-like structures during glucose starvation; USP36, FBL, Midnolin, and BMI1 form a complex responsible for H2Aub degradation. |
Protein interaction screening, Co-IP, knockdown, cell cycle and viability assays |
bioRxivpreprint |
Low |
|