Format

Send to

Choose Destination
Science. 2002 Mar 29;295(5564):2450-2. Epub 2002 Mar 7.

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

Author information

1
Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10/6N-240, 10 Center Drive, Bethesda, MD 20892-1622, USA.

Abstract

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.

PMID:
11884717
DOI:
10.1126/science.1069004
[Indexed for MEDLINE]
Free full text

MeSH terms, Substances

MeSH terms

Substances

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center