Proapoptotic BID is an ATM effector in the DNA-damage response
Proapoptotic BID is an ATM effector in the DNA-damage response
复制标题
DOI：
10.1016/j.cell.2005.06.014
复制
发表时间：
2005-08-26
期刊：
影响因子：
64.5
通讯作者：
Gross, A
中科院分区：
文献类型：
--
作者：
Kamer, I;Sarig, R;Gross, A
“仅BH 3”促凋亡BCL-2家族成员是细胞内损伤的哨兵。在这里，我们证明了BH 3-only BID蛋白在健康细胞中部分定位于细胞核，对于DNA损伤诱导的细胞凋亡是重要的，并且在诱导DNA双链断裂后被磷酸化。我们还发现，BID磷酸化是由ATM激酶介导的，并发生在小鼠BID的两个ATM共识网站。有趣的是，BID-/-细胞在用拓扑异构酶11毒物依托泊苷处理后未能在细胞周期的S期积累;重新引入野生型BID恢复积累。与此相反，引入一个nonphosphorylatable BID突变体没有恢复积累在S期，并导致细胞的敏感性增加依托泊苷诱导的细胞凋亡。这些结果暗示BID作为ATM效应器，并提高了促凋亡BID也可能对S期阻滞发挥重要的促生存作用的可能性。
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 11 poison etoposide; reintroducing wildtype 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.