Nutrient availability regulates SIRT1 through a forkhead-dependent pathway.

Science (New York, N.Y.) ·Vol. 306 ·No. 5704 ·2004-12-17 ·Pages 2105-8

Nemoto S, Fergusson MM, Finkel T

Abstract

Nutrient availability regulates life-span in a wide range of organisms. We demonstrate that in mammalian cells, acute nutrient withdrawal simultaneously augments expression of the SIRT1 deacetylase and activates the Forkhead transcription factor Foxo3a. Knockdown of Foxo3a expression inhibited the starvation-induced increase in SIRT1 expression. Stimulation of SIRT1 transcription by Foxo3a was mediated through two p53 binding sites present in the SIRT1 promoter, and a nutrient-sensitive physical interaction was observed between Foxo3a and p53. SIRT1 expression was not induced in starved p53-deficient mice. Thus, in mammalian cells, p53, Foxo3a, and SIRT1, three proteins separately implicated in aging, constitute a nutrient-sensing pathway.

MeSH Terms

Adipose Tissue/metabolism Animals Binding Sites Culture Media Culture Media, Serum-Free DNA-Binding Proteins/metabolism Forkhead Box Protein O1 Forkhead Transcription Factors Gene Deletion Genes, p53 Glucose HeLa Cells Humans Mice Mice, Inbred C57BL Mutation PC12 Cells Promoter Regions, Genetic RNA, Small Interfering/pharmacology Rats Recombinant Fusion Proteins/metabolism Recombinant Proteins/metabolism Serum Sirtuin 1 Sirtuins/genetics,metabolism Starvation Transcription Factors/metabolism Transcription, Genetic Tumor Suppressor Protein p53/metabolism

Chemicals

Culture Media Culture Media, Serum-Free DNA-Binding Proteins FOXO1 protein, human Forkhead Box Protein O1 Forkhead Transcription Factors RNA, Small Interfering Recombinant Fusion Proteins Recombinant Proteins Transcription Factors Tumor Suppressor Protein p53 Sirt1 protein, mouse Sirt1 protein, rat Sirtuin 1 Sirtuins Glucose

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Nemoto Shino

Cardiovascular Branch, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD 20892, USA.

Fergusson Maria M

Finkel Toren

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1101731

Published

2004-12-17

Pages

2105-8

Language

English

Region

United States

NLM ID

0404511

Subset

External Links

PubMed source DOI: 10.1126/science.1101731 View journal details

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Nutrient availability regulates SIRT1 through a forkhead-dependent pathway.

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