Authors: Ghazi A; Henis-Korenblit S; Kenyon C
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.
Keywords: Animals; Animals, Genetically Modified; Caenorhabditis elegans/*enzymology/genetics/*physiology; Gene Expression Regulation; Longevity/genetics/*physiology; Proteasome Endopeptidase Complex/genetics/*metabolism; Ubiquitin-Protein Ligases/genetics/*metabolism|
Journal: Proceedings of the National Academy of Sciences of the United States of America Volume: 104 Issue: 14 Pages: 5947-52 Date: March 30, 2007 PMID: 17392428 |
Ghazi A, Henis-Korenblit S, Kenyon C (2007) Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proceedings of the National Academy of Sciences of the United States of America 104: 5947-52.
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