ArticleProceedings of the National Academy of Sciences of the United States of America2015
The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.
- DNA methylation signatures of bilateral hippocampal volume, asymmetry and atrophy: a cross-omics analysis in the general population.EBioMedicine · 2026Pooled it
- GNL3 SUMOylation is essential for DNA double-strand break repair by homologous recombination.Nature communications · 2026Article
- Targeting MMA-induced USP36 methylmalonylation to suppress macrophage polarization and tumor progression in clear-cell renal cell carcinoma.Cell death and differentiation · 2026Article
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- DNMT1 methylates E3 ligase FBXO32 to regulate Myc stability and glycolytic reprogramming in diabetic retinopathy associated endothelial cells.Journal of bioenergetics and biomembranes · 2026Article
- Akt-mediated RALY phosphorylation functions as a molecular switch governing c-Myc stability.Cell death and differentiation · 2026Article
- Nucleolar-localized sialidase Neu4 suppresses cell proliferation through destabilizing c-Myc via interacting with ribosomal proteins L5 and L11.Glycoconjugate journal · 2026Article
- Article
- MGMT upregulation mediates Temozolomide resistance conferred USP5 dependency.Scientific reports · 2026Article
- Molecular regulation by ubiquitin-specific proteases (USPs) in HCC: cell cycle, oncogenic signaling, and beyond.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Resveratrol targets mitochondrial USP36-SOD2 to induce autophagy-ferroptosis and inhibit gastric cancer progression.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.Genes & diseases · 2025Review
- RPL22L1-Myc positive feedback loop drives lung adenocarcinoma progression.Cancer cell international · 2025Article
- The deubiquitinase USP36 funtions through catalytic-dependent and catalytic-independent mechanisms in Drosophila.Genetics · 2025Article
- Chemotherapeutic drug-triggered AEP-cleaved G3BP1 orchestrates stress granules/nucleoli/mitochondria in osteosarcoma.Bone research · 2025Article
- Ubiquitination of transcription factors in cancer: unveiling therapeutic potential.Molecular oncology · 2025Review
- Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology.Genes & diseases · 2025Review
- Role of ubiquitin-specific proteases in programmed cell death of breast cancer cells.Genes & diseases · 2025Review
- PDCD11 Stabilizes C-MYC Oncoprotein by Hindering C-MYC-SKP2 Negative Feedback Loop to Facilitate Progression of p53-Mutant Breast and Colon Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Nucleolus: A Central Hub for Ribosome Biogenesis and Cellular Regulatory Signals.International journal of molecular sciences · 2025Review
86 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
c-Myc protein stability and activity are tightly regulated by the ubiquitin-proteasome system. Aberrant stabilization of c-Myc contributes to many human cancers. c-Myc is ubiquitinated by SCF(Fbw7) (a SKP1-cullin-1-F-box complex that contains the F-box and WD repeat domain-containing 7, Fbw7, as the F-box protein) and several other ubiquitin ligases, whereas it is deubiquitinated and stabilized by ubiquitin-specific protease (USP) 28. The bulk of c-Myc degradation appears to occur in the nucleolus. However, whether c-Myc is regulated by deubiquitination in the nucleolus is not known. Here, we report that the nucleolar deubiquitinating enzyme USP36 is a novel c-Myc deubiquitinase. USP36 interacts with and deubiquitinates c-Myc in cells and in vitro, leading to the stabilization of c-Myc. This USP36 regulation of c-Myc occurs in the nucleolus. Interestingly, USP36 interacts with the nucleolar Fbw7γ but not the nucleoplasmic Fbw7α. However, it abolished c-Myc degradation mediated both by Fbw7γ and by Fbw7α. Consistently, knockdown of USP36 reduces the levels of c-Myc and suppresses cell proliferation. We further show that USP36 itself is a c-Myc target gene, suggesting that USP36 and c-Myc form a positive feedback regulatory loop. High expression levels of USP36 are found in a subset of human breast and lung cancers. Altogether, these results identified USP36 as a crucial and bono fide deubiquitinating enzyme controlling c-Myc's nucleolar degradation pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.