Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online April 16, 2009
Science DOI: 10.1126/science.1173507

Reports

Submitted on March 13, 2009
Accepted on April 8, 2009

Proteasomal Regulation of the Hypoxic Response Modulates Aging in C. elegans

Ranjana Mehta 1{dagger}, Katherine A. Steinkraus 1{dagger}, George L. Sutphin 2, Fresnida J. Ramos 1, Lara S. Shamieh 1, Alexander Huh 1, Christina Davis 1, Devon Chandler-Brown 1, Matt Kaeberlein 1*

1 Department of Pathology, University of Washington, Seattle, WA 98195, USA.
2 Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.

* To whom correspondence should be addressed.
Matt Kaeberlein , E-mail: kaeber{at}u.washington.edu

{dagger}These authors contributed equally to this work.

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 amyloid beta 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/IGF-1-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The von Hippel Lindau Tumor Suppressor Limits Longevity.
R.-U. Muller, F. Fabretti, S. Zank, V. Burst, T. Benzing, and B. Schermer (2009)
J. Am. Soc. Nephrol. 20, 2513-2517
   Abstract »    Full Text »    PDF »
Two Distinct Roles for EGL-9 in the Regulation of HIF-1-Mediated Gene Expression in Caenorhabditis elegans.
Z. Shao, Y. Zhang, and J. A. Powell-Coffman (2009)
Genetics 183, 821-829
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)