Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Science. 2009 May 29;324(5931):1196-8. doi: 10.1126/science.1173507. Epub 2009 Apr 16.

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

Author information

  • 1Department of Pathology, University of Washington, Seattle, WA 98195, USA.

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.

PMID:
19372390
[PubMed - indexed for MEDLINE]
PMCID:
PMC2737476
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk