Apoptosis is a regulated form of cell death that proceeds by defined biochemical pathways. Most apoptosis is controlled by interactions between pro-survival and pro-apoptotic Bcl-2 family proteins in which death is often the consequence of permeabilization of the mitochondrial outer membrane. Many drugs affect this equilibrium to favor apoptosis but this process is not completely understood. We show that the chemotherapeutic drug cisplatin initiates an apoptotic pathway by phosphorylation of a pro-survival Bcl-2 family member, Bcl-xL, by cyclin-dependent kinase 2. The phosphorylation occurred at a previously unreported site and its biologic significance was demonstrated by a phosphomimetic modification of Bcl-xL that was able to induce apoptosis without addition of cisplatin. The mechanism of cell death induction was similar to that initiated by pro-apoptotic Bcl-2 family proteins, that is, phosphorylated Bcl-xL translocated to the mitochondrial membrane, and formed pores in the membrane. This initiated cytochrome c release and caspase activation that resulted in cell death.

中文翻译：

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应力后，Bcl-xL的Cdk2磷酸化将其转化为模仿Bax / Bak的促凋亡蛋白。

凋亡是通过确定的生化途径进行的细胞死亡的调节形式。大多数凋亡是由促存活和促凋亡Bcl-2家族蛋白之间的相互作用控制的，其中死亡通常是线粒体外膜透化的结果。许多药物影响这种平衡以促进细胞凋亡，但这一过程尚未完全了解。我们显示化疗药物顺铂通过细胞周期蛋白依赖性激酶2磷酸化前存活的Bcl-2家族成员Bcl-xL引发凋亡途径。磷酸化发生在以前未报道的位点，其生物学意义已通过Bcl-xL的磷酸化修饰，能够在不添加顺铂的情况下诱导细胞凋亡。细胞死亡诱导的机制类似于由凋亡前的Bcl-2家族蛋白引发的机制，即磷酸化的Bcl-xL易位至线粒体膜，并在膜中形成孔。这启动了细胞色素C的释放和胱天蛋白酶的活化，导致细胞死亡。