HIF1-regulated ATRIP expression is required for hypoxia induced ATR activation.
FEBS Lett
; 587(7): 930-5, 2013 Apr 02.
Article
em En
| MEDLINE
| ID: mdl-23454212
ABSTRACT
The ATR-ATRIP protein kinase complex plays a crucial role in the cellular response to replication stress and DNA damage. Recent studies found that ATR could be activated in response to hypoxia and be involved in hypoxia-induced genetic instability in cancer cells. However, the underlying mechanisms for ATR activation in response to hypoxic stress are still not fully understood. We reported that ATRIP is a direct target of HIF-1. Silencing the expression of HIF-1α in cancer cells by RNA interference abolished hypoxia-induced ATRIP expression. Silencing the expression of ATRIP by RNA interference abolished hypoxia induced ATR activation and CHK1 phosphorylation in cancer cells. Taken together, these data shed novel insights on the mechanism of hypoxia-induced activation of the ATR pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
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Proteínas de Ciclo Celular
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Ligação a DNA
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Subunidade alfa do Fator 1 Induzível por Hipóxia
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2013
Tipo de documento:
Article