Research Paper Volume 5, Issue 3 pp 151—154
Sirt1 activation by resveratrol is substrate sequence-selective
- 1 Department of Biochemistry, University of Bayreuth, Bayreuth, Germany
- 2 Department of Enzymology, Institute for Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Germany
Received: February 27, 2013 Accepted: March 6, 2013 Published: March 8, 2013
https://doi.org/10.18632/aging.100542How to Cite
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.
One Sentence Summary
Testing 6802 acetylation sites reveals that resveratrol effects on Sirt1-dependent deacetylation depend on substrate sequence and suggests substrates relevant for in vivo effects.