Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex

Arjumand Ghazi, Sivan Henis-Korenblit, Cynthia Kenyon

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

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.

Original languageEnglish
Pages (from-to)5947-5952
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number14
DOIs
StatePublished - 3 Apr 2007
Externally publishedYes

Keywords

  • Aging
  • Insulin
  • Proteasome
  • Ubiquitin
  • daf-2

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