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Mammalian SIRT1 represses forkhead transcription factors.
- Source :
-
Cell [Cell] 2004 Feb 20; Vol. 116 (4), pp. 551-63. - Publication Year :
- 2004
-
Abstract
- The NAD-dependent deacetylase SIR2 and the forkhead transcription factor DAF-16 regulate lifespan in model organisms, such as yeast and C. elegans. Here we show that the mammalian SIR2 ortholog SIRT1 deacetylates and represses the activity of the forkhead transcription factor Foxo3a and other mammalian forkhead factors. This regulation appears to be in the opposite direction from the genetic interaction of SIR2 with forkhead in C. elegans. By restraining mammalian forkhead proteins, SIRT1 also reduces forkhead-dependent apoptosis. The inhibition of forkhead activity by SIRT1 parallels the effect of this deacetylase on the tumor suppressor p53. We speculate how down-regulating these two classes of damage-responsive mammalian factors may favor long lifespan under certain environmental conditions, such as calorie restriction.
- Subjects :
- Acetylation
Animals
Apoptosis
Blotting, Northern
Blotting, Western
Cell Line
Dose-Response Relationship, Drug
Down-Regulation
Embryo, Mammalian cytology
Forkhead Box Protein O1
Forkhead Transcription Factors
Gene Expression Regulation
Genes, Reporter
HeLa Cells
Histone Acetyltransferases
Histone Deacetylases metabolism
Humans
Mice
Mice, Knockout
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases metabolism
Plasmids metabolism
Precipitin Tests
Protein Binding
Sirtuin 1
Sirtuins metabolism
Stem Cells metabolism
Transcription, Genetic
Tumor Suppressor Protein p53 metabolism
Tumor Suppressor Proteins metabolism
Up-Regulation
p300-CBP Transcription Factors
Acetyltransferases metabolism
Cell Cycle Proteins metabolism
DNA-Binding Proteins metabolism
Histone Deacetylases physiology
Sirtuins physiology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0092-8674
- Volume :
- 116
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 14980222
- Full Text :
- https://doi.org/10.1016/s0092-8674(04)00126-6