Mammalian TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control.
J Biol Chem
; 285(5): 3030-4, 2010 Jan 29.
Article
em En
| MEDLINE
| ID: mdl-19996108
ABSTRACT
Timeless (Tim), a core circadian clock gene in Drosophila, is retained in mammals but has no apparent mammalian circadian clock function. Mammalian TIM is essential for ATR-dependent Chk1 activation and S-phase arrest. We report that TIM is likewise essential for ATM-dependent Chk2-mediated signaling of doxorubicin-induced DNA double strand breaks. TIM depletion attenuates doxorubicin-induced G(2)/M cell cycle arrest and sensitizes cancer cells to doxorubicin-induced cytotoxicity. TIM is, thereby, a potential novel anticancer drug target whose inhibition may enhance the therapeutic cytotoxicity of agents that activate DNA damage pathways as part of their mechanism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Divisão Celular
/
Regulação da Expressão Gênica
/
Fase G2
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
/
Proteínas Supressoras de Tumor
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos