RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination.
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.
Pubmed ID: 17276341 RIS Download
Aging | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Catalysis | Cell Nucleus | Forkhead Transcription Factors | Heat-Shock Response | Hyperthermia, Induced | Larva | Mutation | Phenotype | Polyubiquitin | Protein Binding | Protein Processing, Post-Translational | Protein Transport | RNA, Messenger | Substrate Specificity | Thermodynamics | Transcription Factors | Transcription, Genetic | Transcriptional Activation | Ubiquitin-Protein Ligases