Redox Regulation of Forkhead Proteins Through a p66shc -Dependent Signaling Pathway

American Association for the Advancement of Science (AAAS) - Tập 295 Số 5564 - Trang 2450-2452 - 2002
Shino Nemoto1, Toren Finkel1
1Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10/6N-240, 10 Center Drive, Bethesda, MD 20892-1622, USA.

Tóm tắt

Genetic determinants of longevity include the forkhead-related transcription factor DAF-16 in the worm Caenorhabditis elegans and the p66shc locus in mice. We demonstrate that p66shc regulates intracellular oxidant levels in mammalian cells and that hydrogen peroxide can negatively regulate forkhead activity. In p66shc –/– cells, the activity of the mammalian forkhead homolog FKHRL1 is increased and redox-dependent forkhead inactivation is reduced. In addition, expression of FKHRL1 results in an increase in both hydrogen peroxide scavenging and oxidative stress resistance. These results demonstrate an important functional relation between three distinct elements linked to aging: forkhead proteins, p66shc , and intracellular oxidants.

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We wish to thank M. Greenberg Y. Luo S. G. Rhee L. Lanfrancone and P. G. Pelicci for reagents; S. Gutkind for helpful discussions; and I. Rovira for help with the manuscript and figures. We are particularly grateful for the help of N. J. Holbrook and X. Wang.

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American Association for the Advancement of Science (AAAS)

Tập 295 Số 5564

2450-2452

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