Authors: Berdichevsky A; Viswanathan M; Horvitz HR; Guarente L
Abstract: The longevity of Caenorhabditis elegans is promoted by extra copies of the sir-2.1 gene in a manner dependent on the forkhead transcription factor DAF-16. We identify two C. elegans 14-3-3 proteins as SIR-2.1 binding partners and show that 14-3-3 genes are required for the life-span extension conferred by extra copies of sir-2.1. 14-3-3 proteins are also required for SIR-2.1-induced transcriptional activation of DAF-16 and stress resistance. Following heat stress, SIR-2.1 can bind DAF-16 in a 14-3-3-dependent manner. By contrast, low insulin-like signaling does not promote SIR-2.1/DAF-16 interaction, and sir-2.1 and the 14-3-3 genes are not required for the regulation of life span by the insulin-like signaling pathway. We propose the existence of a stress-dependent pathway in which SIR-2.1 and 14-3-3 act in parallel to the insulin-like pathway to activate DAF-16 and extend life span.
Keywords: 14-3-3 Proteins/*physiology; Animals; Caenorhabditis elegans/*physiology; Caenorhabditis elegans Proteins/*physiology; Heat-Shock Response; Insulin/physiology; Longevity; Oxidative Stress; Protein Binding; Signal Transduction; Sirtuins/*physiology; Transcription Factors/*physiology|
Journal: Cell Volume: 125 Issue: 6 Pages: 1165-77 Date: June 17, 2006 PMID: 16777605 |
Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L (2006) C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell 125: 1165-77.
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