Sirtuin-mediated deacetylation pathway stabilizes Werner syndrome protein

Kahyo, Tomoaki; Mostoslavsky, Raul; Goto, Makoto; Setou, Mitsutoshi

doi:10.1016/j.febslet.2008.06.031

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Volume 582, Issue 17 , Pages 2479-2483, 23 July 2008

Sirtuin-mediated deacetylation pathway stabilizes Werner syndrome protein

Edited by Noboru Mizushima

Tomoaki Kahyo
- Molecular Gerontology Research Group, Mitsubishi Kagaku Institute of Life Sciences (MITILS), Minamiooya, Machida, 194-8511 Tokyo, Japan
Raul Mostoslavsky
- Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
Makoto Goto
- Division of Anti-Ageing and Longevity Sciences, Department of Clinical Engineering, Faculty of Medical Engineering, Toin University of Yokohama, Kurogane-cho, Aoba-ku, Yokohama, 225-8502 Kanagawa, Japan
Mitsutoshi Setou
- Molecular Gerontology Research Group, Mitsubishi Kagaku Institute of Life Sciences (MITILS), Minamiooya, Machida, 194-8511 Tokyo, Japan
- Hamamatsu University School of Medicine, Department of Molecular Anatomy, 1-20-1 Handayama, Hamamatsu, 431-3192 Shizuoka, Japan
- Corresponding author. Address: Hamamatsu University School of Medicine, Department of Molecular Anatomy, 1-20-1 Handayama, Hamamatsu, 431-3192 Shizuoka, Japan. Fax: +81 53 435 2292.

Received 14 April 2008; received in revised form 9 June 2008; accepted 10 June 2008. published online 24 June 2008.

Abstract

Caloric restriction (CR) is known to promote longevity in various species. Sirtuin-mediated deacetylation has been shown to be related to the promotion of longevity in some species. Here, we show that CR of rats led to an increase in the level of Werner syndrome protein (WRN), a recognized DNA repair protein. In addition, CR simultaneously increased the level of SIRT1, a mammalian sirtuin. In HEK293T cells, sirtuin inhibitors decreased the WRN level, and this effect was suppressed by proteasomal inhibitors. Furthermore, we found a decrease in the WRN level in Sirt1-deficient mice. These results indicate that sirtuin-mediated deacetylation stabilizes WRN.