Proapoptotic BID is an ATM effector in the DNA-damage response.
Cell
; 122(4): 593-603, 2005 Aug 26.
Article
em En
| MEDLINE
| ID: mdl-16122426
ABSTRACT
The "BH3-only" proapoptotic BCL-2 family members are sentinels of intracellular damage. Here, we demonstrated that the BH3-only BID protein partially localizes to the nucleus in healthy cells, is important for apoptosis induced by DNA damage, and is phosphorylated following induction of double-strand breaks in DNA. We also found that BID phosphorylation is mediated by the ATM kinase and occurs in mouse BID on two ATM consensus sites. Interestingly, BID-/- cells failed to accumulate in the S phase of the cell cycle following treatment with the topoisomerase II poison etoposide; reintroducing wild-type BID restored accumulation. In contrast, introducing a nonphosphorylatable BID mutant did not restore accumulation in the S phase and resulted in an increase in cellular sensitivity to etoposide-induced apoptosis. These results implicate BID as an ATM effector and raise the possibility that proapoptotic BID may also play a prosurvival role important for S phase arrest.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Proteínas de Transporte
/
Proteínas Serina-Treonina Quinases
/
Apoptose
/
Proteínas de Ciclo Celular
/
Proteínas Supressoras de Tumor
/
Proteínas de Ligação a DNA
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article