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.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Florent M
FM
Martin
Jeffrey S
JS
Friedman
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