PMID:17392428

Citation	Ghazi, A, Henis-Korenblit, S and Kenyon, C (2007) Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc. Natl. Acad. Sci. U.S.A. 104:5947-52
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.
Links	PubMed PMC1851597 Online version:10.1073/pnas.0700638104
Keywords	Animals; Animals, Genetically Modified; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/genetics; Caenorhabditis elegans/physiology; Gene Expression Regulation; Longevity/genetics; Longevity/physiology; Proteasome Endopeptidase Complex/genetics; Proteasome Endopeptidase Complex/metabolism; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism
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