Daf-2

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The daf-2 gene encodes an insulin-like receptor in the worm C. elegans. Mutations in daf-2 have been shown by Cynthia Kenyon to double the lifespan of the worms.[1] The gene is known to regulate reproductive development, ageing, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and also resistance to bacterial pathogens.[2]

DAF-2 is the only insulin/IGF-1 like receptor in the worm. Insulin/IGF-1-like signaling is conserved from worms to humans. DAF-2 acts to negatively regulate the forkhead transcription factor DAF-16 through a phosphorylation cascade. Genetic analysis reveals that DAF-16 is required for daf-2-dependent lifespan extension and dauer formation. When not phosphorylated, DAF-16 is active and present in the nucleus.

References

  1. See publications documenting series of experiments at Cynthia Kenyon lab, in particular, Jennie B. Dorman, Bella Albinder, Terry Shroyer & Cynthia Kenyon, "The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans," Genetics, volume 141, number 4, pages 1399-1406 (1995); and Javier Apfeld & Cynthia Kenyon, "Cell non-autonomy of C. elegans daf-2 function in the regulation of diapause and lifespan," Cell, v. 95, n.2, pp.199-210 (1998).
  2. Minaxi S Gami and Catherine A Wolkow (2006). "Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for pharmacological manipulation of lifespan". Aging Cell. 5 (1).



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