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Proteasomal regulation of the hypoxic response modulates aging in C. elegans.

ABSTRACT: The Caenorhabditis elegans von Hippel-Lindau tumor suppressor homolog VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the hypoxic response by promoting ubiquitination and degradation of the hypoxic response transcription factor HIF-1. Here, we report that loss of VHL-1 significantly increased life span and enhanced resistance to polyglutamine and beta-amyloid toxicity. Deletion of HIF-1 was epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to modulate aging and proteotoxicity. VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway.

SUBMITTER: Mehta R

PROVIDER: S-EPMC2737476 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Proteasomal regulation of the hypoxic response modulates aging in C. elegans.

Mehta Ranjana R Steinkraus Katherine A KA Sutphin George L GL Ramos Fresnida J FJ Shamieh Lara S LS Huh Alexander A Davis Christina C Chandler-Brown Devon D Kaeberlein Matt M

Science (New York, N.Y.) 20090416 5931

The Caenorhabditis elegans von Hippel-Lindau tumor suppressor homolog VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the hypoxic response by promoting ubiquitination and degradation of the hypoxic response transcription factor HIF-1. Here, we report that loss of VHL-1 significantly increased life span and enhanced resistance to polyglutamine and beta-amyloid toxicity. Deletion of HIF-1 was epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to modulate aging and p ...[more]

PMID: 19372390

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