RLE-1, an E3 Ubiquitin Ligase, Regulates C. elegans Aging by Catalyzing DAF-16 Polyubiquitination

Wensheng Li, Beixue Gao, Sang Myeong Lee, Karen Bennett, Deyu Fang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The forkhead transcription factor, DAF-16, a downstream target of the insulin/IGF-I signaling pathway in C. elegans, is indispensable both for lifespan regulation and stress resistance. The molecular mechanisms involved in regulating DAF-16 transcriptional activation remain undefined. Here, we have identified an E3 ubiquitin ligase, RLE-1 (regulation of longevity by E3), which regulates aging in C. elegans. Disruption of RLE-1 expression in C. elegans increases lifespan; this extension of lifespan is due to elevated DAF-16 protein but not to changes of daf-16 mRNA levels. We have also found that RLE-1 catalyzes DAF-16 ubiquitination, leading to degradation by the proteasome. Elimination of RLE-1 expression in C. elegans causes increased transcriptional activation and sustained nuclear localization of DAF-16. Overexpression of DAF-16 in rle-1 mutants increases worm lifespan, while disruption of DAF-16 expression in rle-1 mutants reverses their longevity. Thus, RLE-1 is an E3 ubiquitin ligase of DAF-16 that regulates C. elegans aging.

Original languageEnglish (US)
Pages (from-to)235-246
Number of pages12
JournalDevelopmental Cell
Volume12
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'RLE-1, an E3 Ubiquitin Ligase, Regulates C. elegans Aging by Catalyzing DAF-16 Polyubiquitination'. Together they form a unique fingerprint.

Cite this