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Mech Ageing Dev. 2006 Sep;127(9):741-7. Epub 2006 Jul 24.

C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO.

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  • 1Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01605, USA.

Abstract

14-3-3 proteins are evolutionarily conserved and ubiquitous proteins that function in a wide variety of biological processes. Here we define a new role for C. elegans 14-3-3 proteins in life span regulation. We identify two C. elegans 14-3-3 proteins as interacting proteins of a major life span regulator, the C. elegans SIR2 ortholog, SIR-2.1. Similar to sir-2.1, we find that overexpression of either 14-3-3 protein (PAR-5 or FTT-2) extends life span and that this is dependent on DAF-16, a forkhead transcription factor (FOXO), another important life span regulator in the insulin/IGF-1 signaling pathway. Furthermore, we show that both 14-3-3 proteins are co-expressed with DAF-16 and SIR-2.1 in the tissues critical for life span regulation. Finally, we show that DAF-16/FOXO also physically interacts with the 14-3-3 proteins. These results suggest that C. elegans 14-3-3 proteins can regulate longevity by cooperating with both SIR-2.1 and DAF-16/FOXO.

PMID:
16860373
[PubMed - indexed for MEDLINE]
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