ArticleMolecular and cellular biology2013
The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical ubiquitination.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
- Domain-dependent uncoupling of the co-chaperone and E3 ubiquitin ligase CHIP underlies heterogeneity in spinocerebellar ataxia 48.The Journal of biological chemistry · 2026Article
- Centenarian SIRT6 variants elevate SIRT6 protein and enhance cellular senescence resistance.Research square · 2026Article
- Sirt6 promotes tumor growth and suppresses immune surveillance.Cancer cell international · 2026Article
- CHIP/STUB1 suppresses the transcription and latent reactivation of HIV-1 via the TRAF6-NF-κB-HIV-LTR axis.PLoS pathogens · 2025Article
- Article
- CHIP promotes CAD ubiquitination and degradation to suppress the proliferation and colony formation of glioblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics.International journal of medical sciences · 2024Review
- Article
- Sirtuins at the Crossroads between Mitochondrial Quality Control and Neurodegenerative Diseases: Structure, Regulation, Modifications, and Modulators.Aging and disease · 2023Review
- SIRT6's function in controlling the metabolism of lipids and glucose in diabetic nephropathy.Frontiers in endocrinology · 2023Review
- SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.Aging and disease · 2022Review
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer.Sub-cellular biochemistry · 2022Review
- Article
- CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity.iScience · 2021Article
- Cytoplasmic sirtuin 6 translocation mediated by p62 polyubiquitination plays a critical role in cadmium-induced kidney toxicity.Cell biology and toxicology · 2021Article
- The Two-Faced Role of SIRT6 in Cancer.Cancers · 2021Review
- CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.Molecules and cells · 2021Article
- SIRT6 Protects Smooth Muscle Cells From Senescence and Reduces Atherosclerosis.Circulation research · 2021Article
- Conserved and Unique Roles of Chaperone-Dependent E3 Ubiquitin Ligase CHIP in Plants.Frontiers in plant science · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ubiquitin ligase CHIP (carboxyl terminus of Hsp70-interacting protein) regulates protein quality control, and CHIP deletion accelerates aging and reduces the life span in mice. Here, we reveal a mechanism for CHIP's influence on longevity by demonstrating that CHIP stabilizes the sirtuin family member SirT6, a lysine deacetylase/ADP ribosylase involved in DNA repair, metabolism, and longevity. In CHIP-deficient cells, SirT6 protein half-life is substantially reduced due to increased proteasome-mediated degradation, but CHIP overexpression in these cells increases SirT6 protein expression without affecting SirT6 transcription. CHIP noncanonically ubiquitinates SirT6 at K170, which stabilizes SirT6 and prevents SirT6 canonical ubiquitination by other ubiquitin ligases. In CHIP-depleted cells, SirT6 K170 mutation increases SirT6 half-life and prevents proteasome-mediated degradation. The global decrease in SirT6 expression in the absence of CHIP is associated with decreased SirT6 promoter occupancy, which increases histone acetylation and promotes downstream gene transcription in CHIP-depleted cells. Cells lacking CHIP are hypersensitive to DNA-damaging agents, but DNA repair and cell viability are rescued by enforced expression of SirT6. The discovery of this CHIP-SirT6 interaction represents a novel protein-stabilizing mechanism and defines an intersection between protein quality control and epigenetic regulation to influence pathways that regulate the biology of aging.
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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.