Bok is a genuine multi-BH-domain protein that triggers apoptosis in the absence of Bax and Bak
Bok is a genuine multi-BH-domain protein that triggers apoptosis in the absence of Bax and Bak
复制标题
DOI：
10.1242/jcs.181727
复制
发表时间：
2016-06-01
影响因子：
4
通讯作者：
Essmann, Frank
中科院分区：
文献类型：
--
作者：
Einsele-Scholz, Stephanie;Malmsheimer, Silke;Essmann, Frank
促细胞凋亡多结构域Bcl-2蛋白Bax和巴克（也称为BAK 1）被认为是通过触发细胞色素c的线粒体释放的细胞凋亡内在途径的守门人。然而，第三个β-和Bak-homologous多结构域蛋白Bok的作用仍然没有得到解决。由于Bax和巴克双重缺陷的细胞在很大程度上对各种凋亡刺激具有抗性，因此已经提出，Bok要么是凋亡的抑制剂，要么其作用依赖于Bax和巴克。在这里，我们证明，在几个细胞系统中，博克有效地诱导细胞色素c的释放和细胞凋亡，即使在完全没有巴克和Bax。此外，内源性Bok水平的调节影响细胞凋亡反应。通过RNA干扰和Bok基因的靶向缺失，我们证明Bok可以显著影响卵巢癌细胞对化疗药物的凋亡反应。因此，我们的研究结果不仅确立了Bok作为巴克和Bak非依赖性凋亡诱导剂，而且还表明Bok表达在卵巢癌治疗中的潜在影响。
The pro-apoptotic multidomain Bcl-2 proteins Bax and Bak (also known as BAK1) are considered the gatekeepers of the intrinsic pathway of apoptosis by triggering the mitochondrial release of cytochrome c. The role of the third Bax-and Bak-homologous multidomain protein Bok, however, is still unresolved. As cells doubly deficient for Bax and Bak are largely resistant to various apoptotic stimuli, it has been proposed that Bok is either dispensable for apoptosis or that its role is dependent on Bax and Bak. Here, we demonstrate, in several cell systems, that Bok efficiently induces cytochrome c release and apoptosis even in the complete absence of both Bak and Bax. Moreover, modulation of endogenous Bok levels affects the apoptosis response. By RNA interference and targeted deletion of the Bok gene, we demonstrate that Bok can significantly influence the apoptotic response to chemotherapeutic drugs in ovarian carcinoma cells. Hence, our results not only establish Bok as a Bak- and Bax-independent apoptosis inducer, but also suggest a potential impact of Bok expression in ovarian cancer therapy.