Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway

Shino Nemoto, Toren Finkel

Research output: Contribution to journalArticlepeer-review

704 Scopus citations


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-1 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.

Original languageEnglish (US)
Pages (from-to)2450-2452
Number of pages3
Issue number5564
StatePublished - Mar 29 2002
Externally publishedYes

ASJC Scopus subject areas

  • General


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