CDIP1-BAP31 complex transduces apoptotic signals from endoplasmic reticulum to mitochondria under endoplasmic reticulum stress.
CDIP1-BAP31 complex transduces apoptotic signals from endoplasmic reticulum to mitochondria under endoplasmic reticulum stress.
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DOI：
10.1016/j.celrep.2013.09.020
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发表时间：
2013-10-31
期刊：
影响因子：
8.8
通讯作者：
Lee SW
中科院分区：
文献类型：
--
作者：
Namba T;Tian F;Chu K;Hwang SY;Yoon KW;Byun S;Hiraki M;Mandinova A;Lee SW
已解决的内质网应激反应是维持细胞内动态平衡所必需的，但未解决的内质网应激可导致细胞凋亡。在这里，我们展示了促凋亡的p53靶点CDIP1，作为内质网应激介导的细胞凋亡的关键信号转导。我们确定BAP31，B细胞受体相关蛋白31，作为CDIP1的相互作用伙伴。在内质网应激时，CDIP1被诱导，并增强了与内质网膜上BAP31的结合。我们还表明，CDIP1与BAP31结合是BAP31在内质网应激下被切割和BAP31-Bcl-2结合所必需的。BAP31-CDIP1复合体中的Bcl-2募集以及CDIP1依赖的TBID和caspase-8的激活有助于Bax的寡聚。CDIP1基因敲除导致小鼠对内质网应激诱导的细胞凋亡反应减弱。综上所述，我们的研究结果表明，CDIP1/BAP31介导的线粒体凋亡通路的调控为建立内质网应激介导的细胞凋亡信号的内质网-线粒体信号通路提供了一种新的机制。
Resolved ER stress response is essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. Here, we show that a pro-apoptotic p53 target, CDIP1, acts as a key signal transducer of ER stress-mediated apoptosis. We identify BAP31, B-cell receptor-associated protein 31, as an interacting partner of CDIP1. Upon ER stress, CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31-CDIP1 complex, as well as CDIP1-dependent tBid and caspase-8 activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice leads to impaired response to ER stress-mediated apoptosis. Together, our data demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis pathway represents a novel mechanism for establishing an ER-mitochondrial cross-talk for ER stress-mediated apoptosis signaling.
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影响因子：
64.5
作者：
Wang, Bing;Heath-Engel, Hannah;Shore, Gordon C.
通讯作者：
Shore, Gordon C.
Bax和Bak可以定位于内质网状以启动凋亡。
影响因子：
7.8
作者：
Zong, Wei-Xing;Li, Chi;Hatzivassiliou, Georgia;Lindsten, Tullia;Yu, Qian-Chun;Yuan, Junying;Thompson, Craig B
通讯作者：
Thompson, Craig B
影响因子：
21.3
作者：
Tabas, Ira;Ron, David
通讯作者：
Ron, David
影响因子：
64.8
作者：
Zambrowicz, BP;Friedrich, GA;Sands, AT
通讯作者：
Sands, AT
影响因子：
4.8
作者：
Li, JZ;Lee, B;Lee, AS
通讯作者：
Lee, AS