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


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.

SUBMITTER: Ghazi A 

PROVIDER: S-EPMC1851597 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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

Ghazi Arjumand A   Henis-Korenblit Sivan S   Kenyon Cynthia C  

Proceedings of the National Academy of Sciences of the United States of America 20070328 14


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-sig  ...[more]

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