ArticleThe Journal of biological chemistry2013
Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 372 papers.
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Who cites it
372 citing papers in PubMed, 629 citations in OpenAlex.
- Physiological Significance and Functions of AA.Reviews of physiology, biochemistry and pharmacology · 2027Review
- The sirtuin family: from mechanisms to therapy.Molecular biomedicine · 2026Review
- Regional organization of nutrient absorption across the small intestine.Nature reviews. Gastroenterology & hepatology · 2026Review
- Lipid metabolism and chromatin-associated sirtuin-dependent epigenetic reprogramming in cancer.Molecular biology reports · 2026Review
- Substrate Specificity and Kinetic Mechanism of the NAD+-Dependent Deacylase from Mycobacterium tuberculosis, Rv1151c (Mt-Sirt).Biochemistry · 2026Article
- Article
- Emerging roles of SIRT6 and its modulators in kidney diseases.Cell death discovery · 2026Review
- Mechanistic and functional integration of sirtuin deacylases: from substrate specificity to biological outcomes.Glycoconjugate journal · 2026Review
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- Protein lipidation in cardiovascular homeostasis, development, and disease.Clinical science (London, England : 1979) · 2026Review
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- Development of ratiometric sirtuin fluorescence probes via cleavage of a coumarin dye.Journal of clinical biochemistry and nutrition · 2026Article
- Discovery of 5-(Substituted Phenyl)-2-aryl Benzimidazole Derivatives as SIRT1 Activators: Their Design,Current medicinal chemistry · 2026Article
- Metabolite-driven protein modifications in immune signaling: from established principles to emerging pyruvylation.Frontiers in immunology · 2026Review
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Protein crotonylation in cancer: mechanisms, functions, and therapeutic potential.Cell biology and toxicology · 2025Review
- Sirt6 prevents the age-related decline of HProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Kinetic Analysis of HDAC- and Sirtuin-Mediated Deacylation on Chemically Defined Histones and Nucleosomes.Current protocols · 2025Article
- Structural basis of SIRT2 pre-catalysis NADRSC chemical biology · 2025Article
- Metabolism-driven posttranslational modifications and immune regulation: Emerging targets for immunotherapy.Science advances · 2025Review
312 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mammalian sirtuins (SIRT1 through SIRT7) are members of a highly conserved family of NAD(+)-dependent protein deacetylases that function in metabolism, genome maintenance, and stress responses. Emerging evidence suggests that some sirtuins display substrate specificity toward other acyl groups attached to the lysine ε-amine. SIRT6 was recently reported to preferentially hydrolyze long-chain fatty acyl groups over acetyl groups. Here we investigated the catalytic ability of all sirtuins to hydrolyze 13 different acyl groups from histone H3 peptides, ranging in carbon length, saturation, and chemical diversity. We find that long-chain deacylation is a general feature of mammalian sirtuins, that SIRT1 and SIRT2 act as efficient decrotonylases, and that SIRT1, SIRT2, SIRT3, and SIRT4 can remove lipoic acid. These results provide new insight into sirtuin function and a means for cellular removal of an expanding list of endogenous lysine modifications. Given that SIRT6 is a poor deacetylase in vitro, but binds and prefers to hydrolyze long-chain acylated peptides, we hypothesize that binding of certain free fatty acids (FFAs) could stimulate deacetylation activity. Indeed, we demonstrate that several biologically relevant FFAs (including myristic, oleic, and linoleic acids) at physiological concentrations induce up to a 35-fold increase in catalytic efficiency of SIRT6 but not SIRT1. The activation mechanism is consistent with fatty acid inducing a conformation that binds acetylated H3 with greater affinity. Binding of long-chain FFA and myristoylated H3 peptide is mutually exclusive. We discuss the implications of discovering endogenous, small-molecule activators of SIRT6.
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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.