ArticleThe Journal of biological chemistry2019
The ubiquitin-specific protease USP17 prevents cellular senescence by stabilizing the methyltransferase SET8 and transcriptionally repressing
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- SUMOylation of SETD8 Promotes Tumor Growth by Methylating and Stabilizing MYC in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SET8 inhibition preserves PTEN to attenuate kidney cell apoptosis in cisplatin nephrotoxicity.Cell death & disease · 2025Article
- The Impact of microRNA SNPs on Breast Cancer: Potential Biomarkers for Disease Detection.Molecular biotechnology · 2025Review
- PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation.The EMBO journal · 2024Article
- SET8 is a novel negative regulator of TGF-β signaling in a methylation-independent manner.Scientific reports · 2023Article
- Deubiquitinase USP17 Regulates Osteoblast Differentiation by Increasing Osterix Protein Stability.International journal of molecular sciences · 2023Article
- HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Article
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- Roles for the methyltransferase SETD8 in DNA damage repair.Clinical epigenetics · 2022Review
- Ubiquitin-specific protease 3 attenuates interleukin-1β-mediated chondrocyte senescence by deacetylating forkhead box O-3 via sirtuin-3.Bioengineered · 2022Article
- The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review.Cancer cell international · 2021Review
- Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Periplocin and cardiac glycosides suppress the unfolded protein response.Scientific reports · 2021Article
- Prediction of Human-Bioinformatics and biology insights · 2021Article
- Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway.Antioxidants (Basel, Switzerland) · 2020Article
- Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy.International journal of molecular sciences · 2020Review
- Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence.Cells · 2020Article
- DNA methylation in peripheral blood leukocytes in late onset Alzheimer's disease.Journal of Alzheimer's disease reportsArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain-containing protein 8 (SET8) is the sole enzyme that monomethylates Lys-20 of histone H4 (H4K20). SET8 has been implicated in the regulation of multiple biological processes, such as gene transcription, the cell cycle, and senescence. SET8 quickly undergoes ubiquitination and degradation by several E3 ubiquitin ligases; however, the enzyme that deubiquitinates SET8 has not yet been identified. Here we demonstrated that ubiquitin-specific peptidase 17-like family member (USP17) deubiquitinates and therefore stabilizes the SET8 protein. We observed that USP17 interacts with SET8 and removes polyubiquitin chains from SET8. USP17 knockdown not only decreased SET8 protein levels and H4K20 monomethylation but also increased the levels of the cyclin-dependent kinase inhibitor p21. As a consequence, USP17 knockdown suppressed cell proliferation. We noted that USP17 was down-regulated in replicative senescence and that USP17 inhibition alone was sufficient to trigger cellular senescence. These results reveal a regulatory mechanism whereby USP17 prevents cellular senescence by removing ubiquitin marks from and stabilizing SET8 and transcriptionally repressing
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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.