PIDD-dependent activation of caspase-2-mediated mitochondrial injury in E1A-induced cellular sensitivity to macrophage nitric oxide-induced apoptosis.
PIDD-dependent activation of caspase-2-mediated mitochondrial injury in E1A-induced cellular sensitivity to macrophage nitric oxide-induced apoptosis.
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DOI：
10.1038/s41420-018-0100-3
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发表时间：
2018
影响因子：
7
通讯作者：
Cook JL
中科院分区：
文献类型：
--
作者：
Radke JR;Figueroa I;Routes JM;Cook JL
腺病毒E1 A癌基因的表达通过巨噬细胞产生的肿瘤坏死因子（TNF）-α和一氧化氮（NO）诱导的凋亡使肿瘤细胞对先天性免疫排斥敏感。E1 A通过两种不同的机制使细胞对TNF-α和NO敏感，分别通过抑制NF-κ B依赖的抗凋亡反应和增强caspase-2活化和线粒体损伤。E1 A增强caspase-2激活的机制尚不清楚。在这里，我们报告说，E1 A诱导的敏化NO诱导的细胞凋亡是依赖于PIDD（p53诱导蛋白与死亡结构域）的表达和增强的原发性免疫缺陷病（PIDD）处理形成的PIDDosome，caspase-2激活复合物的核心组成部分。NO诱导的E1 A表达细胞凋亡不需要表达巴克或Bax，表明NO诱导的caspase-2介导的线粒体损伤不通过典型的促凋亡Bcl-2家族成员诱导线粒体细胞色素C释放的活动进行。这些结果定义了一个PIDD依赖性途径，通过E1 A增强Casapse-2介导的线粒体损伤，导致哺乳动物细胞对巨噬细胞诱导的NO介导的凋亡的敏感性增加。
Expression of the adenovirus E1A oncogene sensitizes tumor cells to innate immune rejection by apoptosis induced by macrophage-produced tumor necrosis factor (TNF)-α and nitric oxide (NO). E1A sensitizes cells to TNF-α and NO through two distinct mechanisms, by repressing NF-κB-dependent antiapoptotic responses and enhancing caspase-2 activation and mitochondrial injury, respectively. The mechanisms through which E1A enhances caspase-2 activation in response to NO were unknown. Here, we report that E1A-induced sensitization to NO-induced apoptosis is dependent on expression of PIDD (p53-inducible protein with a death domain) and enhancement of primary immunodeficiency diseases (PIDD) processing for formation of the PIDDosome, the core component of the caspase-2 activation complex. NO-induced apoptosis in E1A-expressing cells did not require expression Bak or Bax, indicating that NO-induced caspase-2-mediated mitochondrial injury does not proceed through the activities of typical, proapoptotic Bcl-2 family members that induce mitochondrial cytochrome C release. These results define a PIDD-dependent pathway, through which E1A enhances casapse-2-mediated mitochondrial injury, resulting in increased sensitivity of mammalian cells to macrophage-induced, NO-mediated apoptosis.
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影响因子：
32.4
作者：
Bronner DN;Abuaita BH;Chen X;Fitzgerald KA;Nuñez G;He Y;Yin XM;O'Riordan MX
通讯作者：
O'Riordan MX
影响因子：
4.6
作者：
Gu ZT;Li L;Wu F;Zhao P;Yang H;Liu YS;Geng Y;Zhao M;Su L
通讯作者：
Su L
DOI：
10.1073/pnas.83.18.6965
发表时间：
1986-09-01
影响因子：
11.1
作者：
COOK, JL;WALKER, TA;PILDER, SH
通讯作者：
PILDER, SH
影响因子：
4.8
作者：
Guo, Y;Srinivasula, SM;Alnemri, ES
通讯作者：
Alnemri, ES
影响因子：
4.8
作者：
Enoksson, M;Robertson, JD;Orrenius, S
通讯作者：
Orrenius, S