Publication Date:
2004-12-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nemoto, Shino -- Fergusson, Maria M -- Finkel, Toren -- New York, N.Y. -- Science. 2004 Dec 17;306(5704):2105-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Branch, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604409" target="_blank"〉PubMed〈/a〉
Keywords:
Adipose Tissue/metabolism
;
Animals
;
Binding Sites
;
Culture Media
;
Culture Media, Serum-Free
;
DNA-Binding Proteins/*metabolism
;
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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