FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP.
Nat Cell Biol
; 8(10): 1064-73, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-16964248
ABSTRACT
FOXO (Forkhead box O) transcription factors are important regulators of cellular metabolism, cell-cycle progression and cell death. FOXO activity is regulated by multiple post-translational modifications, including phosphorylation, acetylation and polyubiquitination. Here, we show that FOXO becomes monoubiquitinated in response to increased cellular oxidative stress, resulting in its re-localization to the nucleus and an increase in its transcriptional activity. Deubiquitination of FOXO requires the deubiquitinating enzyme USP7/HAUSP (herpesvirus-associated ubiquitin-specific protease), which interacts with and deubiquitinates FOXO in response to oxidative stress. Oxidative stress-induced ubiquitination and deubiquitination by USP7 do not influence FOXO protein half-life. However, USP7 does negatively regulate FOXO transcriptional activity towards endogenous promoters. Our results demonstrate a novel mechanism of FOXO regulation and indicate that USP7 has an important role in regulating FOXO-mediated stress responses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endopeptidases
/
Fatores de Transcrição
/
Regulação da Expressão Gênica
/
Ubiquitina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2006
Tipo de documento:
Article