C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span.
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.
Berdichevsky
Ala
A
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, 02139, USA.
Viswanathan
Mohan
M
Horvitz
H Robert
HR
Guarente
Leonard
L
D048948:14-3-3 Proteins / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D051858:Forkhead Transcription Factors; D018869:Heat-Shock Response; D007328:Insulin / Q000502:physiology; D008136:Longevity; D018384:Oxidative Stress; D011485:Protein Binding; D015398:Signal Transduction; D037761:Sirtuins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D048948:14-3-3 Proteins; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C106207:par-5 protein, C elegans; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins