ArticleExperimental & molecular medicine2023
SIRT1 ubiquitination is regulated by opposing activities of APC/C-Cdh1 and AROS during stress-induced premature senescence.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- SIRT1 in Senescence: Mitochondria and Immune Crosstalk.Biology · 2026Review
- APC/C-CDH1 suppresses AROS-mediated protection against DNA damage-induced senescence by ubiquitination.BMB reports · 2026Article
- Fibrillarin Resists Cellular Senescence Via SIRT1-Dependent Nicotinamide Metabolism and Its Inhibition Sensitizes Senolytic Therapy in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Function-Centric Framework for Mitochondrial Quality Control.Biomolecules · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Red ginseng-derived components attenuate UVB-induced keratinocyte senescence via senomorphic mechanisms.Journal of ginseng research · 2026Article
- Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- SIRT1 deficiency promotes age-related heart failure through enhancing ferroptosis via GATA4-HADHA-GPX4 axis.Cell death & disease · 2026Article
- Sirtuin 1 is a key molecular link between cellular senescence and heart failure.Frontiers in molecular medicine · 2026Review
- Discovery of 5-(Substituted Phenyl)-2-aryl Benzimidazole Derivatives as SIRT1 Activators: Their Design,Current medicinal chemistry · 2026Article
- A SENP7-SIRT1-IL-10 Axis Driven by DeSUMOylation Promotes Breg Differentiation and Immune Evasion in Colorectal Cancer.International journal of biological sciences · 2026Article
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- Ubiquitination regulation of mitochondrial homeostasis: a new sight for the treatment of gastrointestinal tumors.Frontiers in immunology · 2025Review
- RNA sequencing-based profiling of differentially expressed microRNAs in endothelial cells from offspring of hypertensive pregnancies: a preliminary study.Frontiers in molecular biosciences · 2025Article
- USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling.Nature communications · 2024Article
- Stress Hormones: Unveiling the Role in Accelerated Cellular Senescence.Aging and disease · 2024Review
- Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16Cell communication and signaling : CCS · 2024Article
- Crosstalk of ubiquitin system and non-coding RNA in fibrosis.International journal of biological sciences · 2024Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SIRT1, a member of the mammalian sirtuin family, is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase with key roles in aging-related diseases and cellular senescence. However, the mechanism by which SIRT1 protein homeostasis is controlled under senescent conditions remains elusive. Here, we revealed that SIRT1 protein is significantly downregulated due to ubiquitin-mediated proteasomal degradation during stress-induced premature senescence (SIPS) and that SIRT1 physically associates with anaphase-promoting complex/cyclosome (APC/C), a multisubunit E3 ubiquitin ligase. Ubiquitin-dependent SIRT1 degradation is stimulated by the APC/C coactivator Cdh1 and not by the coactivator Cdc20. We found that Cdh1 depletion impaired the SIPS-promoted downregulation of SIRT1 expression and reduced cellular senescence, likely through SIRT1-driven p53 inactivation. In contrast, AROS, a SIRT1 activator, reversed the SIRT1 degradation induced by diverse stressors and antagonized Cdh1 function through competitive interactions with SIRT1. Furthermore, our data indicate opposite roles for Cdh1 and AROS in the epigenetic regulation of the senescence-associated secretory phenotype genes IL-6 and IL-8. Finally, we demonstrated that pinosylvin restores downregulated AROS (and SIRT1) expression levels in bleomycin-induced mouse pulmonary senescent tissue while repressing bleomycin-promoted Cdh1 expression. Overall, our study provides the first evidence of the reciprocal regulation of SIRT1 stability by APC/C-Cdh1 and AROS during stress-induced premature senescence, and our findings suggest pinosylvin as a potential senolytic agent for pulmonary fibrosis.
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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 Socratic graph.