Proteasomal regulation of the hypoxic response modulates aging in C. elegans.
Science
; 324(5931): 1196-8, 2009 May 29.
Article
em En
| MEDLINE
| ID: mdl-19372390
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Fatores de Transcrição
/
Envelhecimento
/
Caenorhabditis elegans
/
Proteínas de Caenorhabditis elegans
/
Proteínas Culina
/
Complexo de Endopeptidases do Proteassoma
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article