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

Science (New York, N.Y.) | May 29, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19372390

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.

Pubmed ID: 19372390 RIS Download

Mesh terms: Aging | Amyloid beta-Peptides | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Caloric Restriction | Cullin Proteins | Female | Fertility | Gene Expression Regulation | Homeostasis | Insulin | Longevity | Male | Models, Animal | Oxygen | Peptides | Proteasome Endopeptidase Complex | RNA Interference | Receptor, Insulin | Signal Transduction | Transcription Factors | Ubiquitination

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Associated grants

  • Agency: NIA NIH HHS, Id: 1R01AG031108-01
  • Agency: NIA NIH HHS, Id: P30AG013280
  • Agency: NIA NIH HHS, Id: R01 AG031108
  • Agency: NIA NIH HHS, Id: R01 AG031108-01A1

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