ArticleNucleic acids research2019
SIRT6 transcriptionally regulates global protein synthesis through transcription factor Sp1 independent of its deacetylase activity.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 64 citations in OpenAlex.
- Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- SIRT6 alleviates ischemic injury via orchestrating the RREB1/Snail and STC1/Smad7 signaling pathways to regulate endothelial-mesenchymal transition.Science China. Life sciences · 2026Article
- USP11 alleviates pathological cardiac hypertrophy via stabilizing SIRT6.Cellular and molecular life sciences : CMLS · 2026Article
- Sirtuin 2 inhibits global protein synthesis via Rheb-GTPase degradation.EMBO reports · 2026Article
- Article
- Sirt6 prevents the age-related decline of HProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pharmacological activation of SIRT6 suppresses progression of head and neck and esophageal squamous cell carcinoma by modulation of cellular metabolism and protein translation.Cell death & disease · 2025Article
- Atrial Cardiomyopathy-associated Arrhythmia and the Impact of Sirtuin Signaling Pathway: A Narrative Review.Current vascular pharmacology · 2025Review
- Expression analysis and mapping of Viral-Host Protein interactions of Poxviridae suggests a lead candidate molecule targeting Mpox.BMC infectious diseases · 2024Article
- Activation of SIRT6 Deacetylation by DNA Strand Breaks.ACS omega · 2023Article
- Modulation of SIRT6 activity acts as an emerging therapeutic implication for pathological disorders in the skeletal system.Genes & diseases · 2023Review
- The role of mammalian Sirtuin 6 in cardiovascular diseases and diabetes mellitus.Frontiers in physiology · 2023Review
- Review
- SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.Aging and disease · 2022Review
- Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling.Nature communications · 2022Article
- Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis.Experimental & molecular medicine · 2022Article
- Energy restriction induced SIRT6 inhibits microglia activation and promotes angiogenesis in cerebral ischemia via transcriptional inhibition of TXNIP.Cell death & disease · 2022Article
- Sirt6 regulates lifespan inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer.Sub-cellular biochemistry · 2022Review
- Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4.Aging cell · 2021Article
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Global protein synthesis is emerging as an important player in the context of aging and age-related diseases. However, the intricate molecular networks that regulate protein synthesis are poorly understood. Here, we report that SIRT6, a nuclear-localized histone deacetylase represses global protein synthesis by transcriptionally regulating mTOR signalling via the transcription factor Sp1, independent of its deacetylase activity. Our results suggest that SIRT6 deficiency increases protein synthesis in mice. Further, multiple lines of in vitro evidence suggest that SIRT6 negatively regulates protein synthesis in a cell-autonomous fashion and independent of its catalytic activity. Mechanistically, SIRT6 binds to the zinc finger DNA binding domain of Sp1 and represses its activity. SIRT6 deficiency increased the occupancy of Sp1 at key mTOR signalling gene promoters resulting in enhanced expression of these genes and activation of the mTOR signalling pathway. Interestingly, inhibition of either mTOR or Sp1 abrogated the increased protein synthesis observed under SIRT6 deficient conditions. Moreover, pharmacological inhibition of mTOR restored cardiac function in muscle-specific SIRT6 knockout mice, which spontaneously develop cardiac hypertrophy. Overall, these findings have unravelled a new layer of regulation of global protein synthesis by SIRT6, which can be potentially targeted to combat aging-associated diseases like cardiac hypertrophy.
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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.