title: Sirt1 activation by resveratrol is substrate sequence-selective.
abstract: Sirtuins are protein deacetylases used as therapeutic targets. Pharmacological Sirt1 activation has been questioned since the in vitro activator resveratrol failed to stimulate deacetylation of several physiological substrates. We tested the influence of substrate sequence by analyzing resveratrol effects on Sirt1-dependent deacetylation of 6802 physiological acetylation sites using peptide microarrays. Resveratrol stimulated deacetylation of a small set of sites and inhibited deacetylation of another set, whereas most substrates were hardly affected. Solution assays confirmed these substrate categories, and statistical analysis revealed their sequence features. Our results reveal substrate sequence dependence for Sirt1 modulation and suggest substrates contributing to resveratrol effects.
authors.affiliation: Department of Biochemistry, University of Bayreuth, Bayreuth, Germany.
authors.forename: Mahadevan
authors.initials: M
authors.lastname: Lakshminarasimhan
authors.forename: David
authors.initials: D
authors.lastname: Rauh
authors.forename: Mike
authors.initials: M
authors.lastname: Schutkowski
authors.forename: Clemens
authors.initials: C
authors.lastname: Steegborn
mesh_terms: D000107:Acetylation / Q000187:drug effects; D006801:Humans; D046228:Microarray Analysis; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol