RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination.

Authors: Li W; Gao B; Lee SM; Bennett K; Fang D

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.

Keywords: Aging/*metabolism; Animals; Caenorhabditis elegans/*enzymology/*physiology; Caenorhabditis elegans Proteins/genetics/*metabolism; Catalysis; Cell Nucleus/metabolism; Heat-Shock Response; Hyperthermia, Induced; Larva; Mutation/genetics; Phenotype; Polyubiquitin/*metabolism; Protein Binding; Protein Processing, Post-Translational; Protein Transport; RNA, Messenger/genetics/metabolism; Substrate Specificity; Thermodynamics; Transcription Factors/genetics/*metabolism; Transcription, Genetic; Transcriptional Activation/genetics; Ubiquitin-Protein Ligases/*metabolism
Journal: Developmental cell
Volume: 12
Issue: 2
Pages: 235-46
Date: Feb. 6, 2007
PMID: 17276341
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Citation:

Li W, Gao B, Lee SM, Bennett K, Fang D (2007) RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. Developmental cell 12: 235-46.


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