Cited by 140Genetics, Aging, and Longevity in Model OrganismsUbiquitin and proteasome pathwaysFOXO transcription factor regulation

Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex

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Ghazi, Arjumand, Henis-Korenblit, Sivan, Kenyon, Cynthia·2007·Proceedings of the National Academy of Sciences

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.

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  • Mutations in the genes of the CUL-1 E3 ligase complex shorten the extended lifespan of different insulin signaling C. elegans mutants.

    “mutations in the genes of the CUL-1 E3 ligase complex shorten the extended lifespan of different insulin signaling C. elegans mutants (Ghazi et al., 2007)”

    From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Ghazi et al., 2007

    The Results report that RNAi depletion of cul-1 and skr-1/2 shortened the extended lifespan of several daf-2 mutant strains, and that a lin-23 mutation reduced lifespan extension in daf-2 mutants. The claim captures the lifespan finding but overstates the mutation evidence: the paper tested mutations in one CUL-1 complex gene, while it used RNAi to reduce the others. (LLM, conf=0.86)

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Research works printed but not linked: 1

  1. NoteAddedinProof. Whilethis study was in press, Li et al . (39) published results identifying an E3 ligase that affects aging in an opposite fashion.

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Authors
Ghazi, A., Henis-Korenblit, S., & Kenyon, C.
Affiliations
  • University of California, San Francisco (US)
  • Department of Biochemistry and Biophysics, University of California, Mission Bay Genentech Hall, 600 16th Street, San Francisco, CA 94158
Corresponding author
Kenyon, Cynthia
Venue
Proceedings of the National Academy of Sciences
Published
2007-04-03
Volume
104
Issue
14
Pages
5947-5952
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2047102030
Cited by
134
References
40
Citations by year
2026: 4 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 10 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 11 · 2015: 6 · 2014: 10 · 2013: 7 · 2012: 10
FWCI
2.78
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Larry L. Hillblom Foundation
  • National Institutes of Health
  • National Institute on Aging (R01AG011816)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Keywords
Caenorhabditis elegans, lifespan extension, proteasome, E3 ubiquitin ligase, insulin/IGF-1 signaling, DAF-16/FOXO, aging, protein degradation, longevity genes, transcriptional regulation
MeSH terms
Animals, Gene Expression Regulation, Longevity, Caenorhabditis elegans, Animals, Genetically Modified, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex

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