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.
Li
Wensheng
W
Department of Otolaryngology-Head & Neck Surgery, University of Missouri School of Medicine, One Hospital Dr., Columbia, MO 65212, USA.
Gao
Beixue
B
Lee
Sang-Myeong
SM
Bennett
Karen
K
Fang
Deyu
D
D000375:Aging / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018869:Heat-Shock Response; D006979:Hyperthermia, Induced; D007814:Larva; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D025821:Polyubiquitin / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D025821:Polyubiquitin; C518005:RLE-1 protein, C elegans; D044767:Ubiquitin-Protein Ligases