Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation
Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation
复制标题
DOI：
10.1101/gad.1093903
复制
发表时间：
2003-06-15
影响因子：
10.5
通讯作者：
Wang, XD
中科院分区：
文献类型：
--
作者：
Nijhawan, D;Fang, M;Wang, XD
紫外线（UV）照射海拉细胞会引发一种由线粒体介导的凋亡反应。对这种反应的生化分析表明，细胞色素c从线粒体释放以及随后的半胱天冬酶激活需要消除胞质抑制剂。这些抑制剂被发现是Mcl - 1和Bcl - x（L），它们是Bcl - 2家族的两个抗凋亡成员。在紫外线处理后，Mcl - 1蛋白合成受阻，现有的Mcl - 1蛋白池被蛋白酶体迅速降解，并且胞质中的Bcl - x（L）转移到线粒体。这些事件是有先后顺序的；Bcl - x（L）的转移需要Mcl - 1的消除。Mcl - 1的消失对于其他线粒体凋亡事件也是必需的，包括Bax转移、细胞色素c释放和半胱天冬酶激活。
Ultraviolet (UV) irradiation of HeLa cells triggers an apoptotic response mediated by mitochondria. Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors were found to be Mcl-1 and Bcl-x(L), two antiapoptotic members of the Bcl-2 family. Following UV treatment, Mcl-1 protein synthesis is blocked, the existing pool of Mcl-1 protein is rapidly degraded by the proteasome, and cytosolic Bcl-x(L) translocates to the mitochondria. These events are sequential; the elimination of Mcl-1 is required for the translocation of Bcl-x(L). The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation.