Regulation of SIRT1 protein levels by nutrient availability

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

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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.

Original languageEnglish
Pages (from-to)2417-2423
Number of pages7
JournalFEBS Letters
Volume582
Issue number16
DOIs
StatePublished - 9 Jul 2008

Bibliographical note

Funding Information:
We thank members of the Cohen lab for helpful comments on the manuscript, and Prof. Moshe Oren (Weizmann Institute of Science, Rehovot, Israel) for the p53 −/− mice. This study was supported by grants from the Israeli Academy of Sciences, German–Israeli Foundation, Binational US–Israel Science Foundation, Israel Cancer Association, Koret Foundation, and the Israel Cancer Research Fund. H.C. is funded by the Alon Foundation.

Funding

We thank members of the Cohen lab for helpful comments on the manuscript, and Prof. Moshe Oren (Weizmann Institute of Science, Rehovot, Israel) for the p53 −/− mice. This study was supported by grants from the Israeli Academy of Sciences, German–Israeli Foundation, Binational US–Israel Science Foundation, Israel Cancer Association, Koret Foundation, and the Israel Cancer Research Fund. H.C. is funded by the Alon Foundation.

FundersFunder number
Israeli Academy of Sciences
Alcon Foundation
Koret Foundation
Israel Cancer Research Fund
German-Israeli Foundation for Scientific Research and Development
United States-Israel Binational Science Foundation
Israel Cancer Association

    Keywords

    • Nutrient availability
    • SIRT1
    • Sirtuins

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