Research Paper|Volume 5, Issue 3|pp 151—154

Sirt1 activation by resveratrol is substrate sequence-selective

Mahadevan Lakshminarasimhan¹, David Rauh², Mike Schutkowski², Clemens Steegborn¹

¹Department of Biochemistry, University of Bayreuth, Bayreuth, Germany
²Department of Enzymology, Institute for Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Germany

Received: February 27, 2013Accepted: March 6, 2013Published: March 8, 2013

Copyright: © 2013 Lakshminarasimhan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.