Mcl-1 Integrates the Opposing Actions of Signaling Pathways That Mediate Survival and Apoptosis
Mcl-1 Integrates the Opposing Actions of Signaling Pathways That Mediate Survival and Apoptosis
复制标题
DOI：
10.1128/mcb.00279-09
复制
发表时间：
2009-07-01
影响因子：
5.3
通讯作者：
Davis, Roger J.
中科院分区：
文献类型：
--
作者：
Morel, Caroline;Carlson, Scott M.;Davis, Roger J.
Mcl-1是Bcl 2相关蛋白家族的成员，其是细胞存活的关键介质。细胞暴露于应激导致Mcl-1 mRNA翻译的抑制和Mcl-1蛋白的快速破坏，这是通过由Mcl-1的糖原合成酶激酶3（GSK 3）磷酸化产生的磷酸降解决定子介导的蛋白酶体降解实现的。在这里，我们证明了先前的磷酸化Mcl-1的c-Jun N-末端蛋白激酶（JNK）是必不可少的Mcl-1磷酸化的GSK 3。因此，应激诱导的Mcl-1降解需要JNK和GSK 3的协调活性。总之，这些数据确定Mcl-1作为JNK的促凋亡活性和抑制GSK 3的AKT途径的促存活活性之间的信号整合位点发挥作用。
Mcl-1 is a member of the Bcl2-related protein family that is a critical mediator of cell survival. Exposure of cells to stress causes inhibition of Mcl-1 mRNA translation and rapid destruction of Mcl-1 protein by proteasomal degradation mediated by a phosphodegron created by glycogen synthase kinase 3 (GSK3) phosphorylation of Mcl-1. Here we demonstrate that prior phosphorylation of Mcl-1 by the c-Jun N-terminal protein kinase (JNK) is essential for Mcl-1 phosphorylation by GSK3. Stress-induced Mcl-1 degradation therefore requires the coordinated activity of JNK and GSK3. Together, these data establish that Mcl-1 functions as a site of signal integration between the proapoptotic activity of JNK and the prosurvival activity of the AKT pathway that inhibits GSK3.