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Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5947-52. Epub 2007 Mar 28.

Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex.

Author information

1
Department of Biochemistry and Biophysics, University of California, Mission Bay Genentech Hall, 600 16th Street, San Francisco, CA 94158, USA.

Abstract

The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

PMID:
17392428
PMCID:
PMC1851597
DOI:
10.1073/pnas.0700638104
[Indexed for MEDLINE]
Free PMC Article

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