BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation.
BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation.
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DOI：
10.1016/j.cell.2016.02.026
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发表时间：
2016-04-07
期刊：
影响因子：
64.5
通讯作者：
Green, Douglas R.
中科院分区：
文献类型：
--
作者：
Llambi, Fabien;Wang, Yue-Ming;Victor, Bernadette;Yang, Mao;Schneider, Desiree M.;Gingras, Sebastien;Parsons, Melissa J.;Zheng, Janet H.;Brown, Scott A.;Pelletier, Stephane;Moldoveanu, Tudor;Chen, Taosheng;Green, Douglas R.
细胞凋亡的线粒体途径由线粒体外膜透化（MOMP）启动。BCL-2家族效应子BAX和巴克被认为是这一过程绝对需要的。在这里，我们报告说，BCL-2卵巢杀伤细胞（BOK）是一个真正的，但非传统的效应MOMP，可以触发细胞凋亡的BAX和巴克的情况下。然而，与经典效应物不同，BOK似乎是组成型活性的，并且对抗凋亡BCL-2蛋白的拮抗作用无反应。相反，BOK在蛋白质稳定性水平上受内质网相关降解途径组分的控制。BOK被AMFR/gp 78 E3泛素连接酶复合物泛素化，并以VCP/p97依赖性方式靶向蛋白酶体降解，从而使细胞存活。当蛋白酶体功能、VCP或gp 78活性受损时，BOK稳定以独立于其他BCL-2蛋白诱导MOMP和凋亡。
The mitochondrial pathway of apoptosis is initiated by mitochondrial outer membrane permeabilization (MOMP). The BCL-2 family effectors BAX and BAK are thought to be absolute required for this process. Here we report that BCL-2 ovarian killer (BOK) is a bona fide yet unconventional effector of MOMP that can trigger apoptosis in the absence of both BAX and BAK. However, unlike the canonical effectors, BOK appears to be constitutively active and unresponsive to antagonistic effects of the antiapoptotic BCL-2 proteins. Rather, BOK is controlled at the level of protein stability by components of the endoplasmic reticulum–associated degradation pathway. BOK is ubiquitylated by the AMFR/gp78 E3 ubiquitin ligase complex and targeted for proteasomal degradation in a VCP/p97-dependent manner, which allows survival of the cell. When proteasome function, VCP, or gp78 activity is compromised, BOK is stabilized to induce MOMP and apoptosis independently of other BCL-2 proteins.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.90.10.4616
发表时间：
1993-05-15
影响因子：
11.1
作者：
DEVER, TE;CHEN, JJ;HINNEBUSCH, AG
通讯作者：
HINNEBUSCH, AG
影响因子：
12.4
作者：
Echeverry, N.;Bachmann, D.;Kaufmann, T.
通讯作者：
Kaufmann, T.
影响因子：
16
作者：
Harding, HP;Zhang, YH;Ron, D
通讯作者：
Ron, D
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D