BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program.
BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program.
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DOI：
10.1126/science.1190217
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发表时间：
2010-12-03
期刊：
影响因子：
--
通讯作者：
Cheng EH
中科院分区：
文献类型：
--
作者：
Ren D;Tu HC;Kim H;Wang GX;Bean GR;Takeuchi O;Jeffers JR;Zambetti GP;Hsieh JJ;Cheng EH
虽然蛋白质BAX和巴克是启动线粒体凋亡所必需的，但BAX和巴克如何被激活仍不清楚。我们提供了体内证据，证明了蛋白质BID、BIM和BATA在激活BAX和巴克中的重要作用。Bid、Bim和Puma三重基因敲除小鼠表现出与Bax和巴克缺乏相关的相同发育缺陷，包括持续的趾间蹼和阴道闭锁。Bid、Bim和Puma的基因缺失阻止了BAX和巴克的同源寡聚化，从而阻止了细胞色素c介导的响应于神经元和T淋巴细胞中的不同死亡信号的半胱天冬酶的激活，尽管存在其他仅BH3分子。因此，许多形式的细胞凋亡需要通过BID、BIM或BIA蛋白家族的成员在线粒体处直接激活BAX和巴克。
Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in vivo evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c-mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins.
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Bax缺失进一步命令小脑颗粒细胞中的细胞死亡途径，并提出了与caspase无关的细胞死亡途径。
影响因子：
7.8
作者：
Miller, T M;Moulder, K L;Knudson, C M;Creedon, D J;Deshmukh, M;Korsmeyer, S J;Johnson, E M Jr
通讯作者：
Johnson, E M Jr
影响因子：
50.3
作者：
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通讯作者：
Letai, Anthony
影响因子：
7.8
作者：
Besirli, CG;Wagner, EF;Johnson, EM
通讯作者：
Johnson, EM
影响因子：
16
作者：
Cheng, EHYA;Wei, MC;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
64.8
作者：
Gavathiotis, Evripidis;Suzuki, Motoshi;Davis, Marguerite L.;Pitter, Kenneth;Bird, Gregory H.;Katz, Samuel G.;Tu, Ho-Chou;Kim, Hyungjin;Cheng, Emily H. -Y.;Tjandra, Nico;Walensky, Loren D.
通讯作者：
Walensky, Loren D.