C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span

Cell. 2006 Jun 16;125(6):1165-77. doi: 10.1016/j.cell.2006.04.036.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / physiology*
  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / physiology*
  • Forkhead Transcription Factors
  • Heat-Shock Response
  • Insulin / physiology
  • Longevity
  • Oxidative Stress
  • Protein Binding
  • Signal Transduction
  • Sirtuins / physiology*
  • Transcription Factors / physiology*


  • 14-3-3 Proteins
  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • Transcription Factors
  • daf-16 protein, C elegans
  • par-5 protein, C elegans
  • SIR-2.1 protein, C elegans
  • Sirtuins