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

doi:10.1016/j.devcel.2006.12.002

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

Pathology

Research output: Contribution to journal › Article › peer-review

102 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 language	English (US)
Pages (from-to)	235-246
Number of pages	12
Journal	Developmental Cell
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/j.devcel.2006.12.002
State	Published - Feb 2007

Keywords

PROTEINS

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
Molecular Biology
Cell Biology
Developmental Biology

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10.1016/j.devcel.2006.12.002

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

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 = "PROTEINS",

author = "Wensheng Li and Beixue Gao and Lee, {Sang Myeong} and Karen Bennett and Deyu Fang",

note = "Funding Information: We thank Dr. Laurent Segalat (University of Lyon, Lyon, France) for the cxTi510 animals and members of the Fang laboratory for constructive comments. We thank the unknown reviewers for their valuable suggestions. We also thank the Caenorhabditis Genetics Center, supported by National Institutes of Health funds, for the C. elegans strains used in this study. ",

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AU - Bennett, Karen

AU - Fang, Deyu

N1 - Funding Information: We thank Dr. Laurent Segalat (University of Lyon, Lyon, France) for the cxTi510 animals and members of the Fang laboratory for constructive comments. We thank the unknown reviewers for their valuable suggestions. We also thank the Caenorhabditis Genetics Center, supported by National Institutes of Health funds, for the C. elegans strains used in this study.

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N2 - 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.

AB - 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.

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

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