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Mammalian SIRT1 represses forkhead transcription factors.
Cell. 2004 Feb 20; 116(4):551-63.Cell

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.

Authors+Show Affiliations

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14980222

Citation

Motta, Maria Carla, et al. "Mammalian SIRT1 Represses Forkhead Transcription Factors." Cell, vol. 116, no. 4, 2004, pp. 551-63.
Motta MC, Divecha N, Lemieux M, et al. Mammalian SIRT1 represses forkhead transcription factors. Cell. 2004;116(4):551-63.
Motta, M. C., Divecha, N., Lemieux, M., Kamel, C., Chen, D., Gu, W., Bultsma, Y., McBurney, M., & Guarente, L. (2004). Mammalian SIRT1 represses forkhead transcription factors. Cell, 116(4), 551-63.
Motta MC, et al. Mammalian SIRT1 Represses Forkhead Transcription Factors. Cell. 2004 Feb 20;116(4):551-63. PubMed PMID: 14980222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mammalian SIRT1 represses forkhead transcription factors. AU - Motta,Maria Carla, AU - Divecha,Nullin, AU - Lemieux,Madeleine, AU - Kamel,Christopher, AU - Chen,Delin, AU - Gu,Wei, AU - Bultsma,Yvette, AU - McBurney,Michael, AU - Guarente,Leonard, PY - 2003/11/18/received PY - 2004/01/20/revised PY - 2004/01/28/accepted PY - 2004/2/26/pubmed PY - 2004/4/16/medline PY - 2004/2/26/entrez SP - 551 EP - 63 JF - Cell JO - Cell VL - 116 IS - 4 N2 - 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. SN - 0092-8674 UR - https://www.unboundmedicine.com/medline/citation/14980222/Mammalian_SIRT1_represses_forkhead_transcription_factors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092867404001266 DB - PRIME DP - Unbound Medicine ER -