Regulation of SIRT1 protein levels by nutrient availability

Kanfi, Yariv; Peshti, Victoria; Gozlan, Yosi M.; Rathaus, Moran; Gil, Reuven; Cohen, Haim Y.

doi:10.1016/j.febslet.2008.06.005

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Volume 582, Issue 16 , Pages 2417-2423, 9 July 2008

Regulation of SIRT1 protein levels by nutrient availability

Edited by Noboru Mizushima

The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel

Received 9 April 2008; received in revised form 22 May 2008; accepted 3 June 2008. published online 09 June 2008.

Abstract

The mammalian NAD+ dependent deacetylase, SIRT1, was shown to be a key protein in regulating glucose homeostasis, and was implicated in the response to calorie restriction. We show here that levels of SIRT1 increased in response to nutrient deprivation in cultured cells, and in multiple tissues of mice after fasting. The increase in SIRT1 levels was due to stabilization of SIRT1 protein, and not an increase in SIRT1 mRNA. In addition, p53 negatively regulated SIRT1 levels under normal growth conditions and is also required for the elevation of SIRT1 under limited nutrient conditions. These results have important implications on the relationship between sirtuins, nutrient availability and aging.

Keywords: SIRT1, Sirtuins, Nutrient availability