Ticking fast or ticking slow, through Shc must you go?
Circumstantial evidence places the p66 isoform of the adapter protein Shc in a position to mediate the accelerated aging phenotype displayed by mice expressing shortened forms of the tumor suppressor protein p53. We present a model in which p66(shc) may be responsible for integrating signals from the p53 pathway with signals from the insulin-like growth factor-1/Daf pathway in mammals. A full understanding of how interactions between p53 and p66(shc) affect longevity will require the production of animals with mutations in the genes encoding both proteins.
Martin
Florent M
FM
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Friedman
Jeffrey S
JS
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology; D008136:Longevity / Q000235:genetics; D051379:Mice; D017526:Receptor, IGF Type 1 / Q000378:metabolism / Q000502:physiology; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1