TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3.
TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3.
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RIP3缺失时TRADD介导肿瘤坏死因子诱导的L929细胞凋亡
DOI：
10.1038/s41598-017-16390-6
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发表时间：
2017-11-23
影响因子：
4.6
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Chang X;Wang L;Wang Z;Wu S;Zhu X;Hu S;Wang Y;Yu J;Chen G
受体相互作用蛋白激酶3（Receptor-interacting protein kinase 3，RIP 3）是介导肿瘤坏死因子α（tumor necrosis factor alpha，TNFα）诱导的L929细胞坏死性凋亡的关键起始因子，因此敲低RIP 3可抑制TNFα诱导的L929细胞坏死性凋亡。然而，在其他研究中，RIP 3敲低显示在L929细胞中将TNFα诱导的坏死性凋亡转变为凋亡。因此，RIP 3敲低是否能阻断TNFα诱导的L929细胞死亡仍存在争议。在本研究中，TNFα激活caspase通路并诱导RIP 3基因敲减的L929细胞死亡，而RIP 3非依赖性细胞死亡可被Z-VAD-FMK（pan-caspase inhibitor）或caspase 8基因敲减所阻断，表明RIP 3基因敲减可将TNFα诱导的坏死性凋亡转变为caspase依赖性凋亡。尽管已报道TNF受体1型相关死亡结构域蛋白（TRADD）和RIP 1均可介导TNFα诱导的细胞凋亡，但TRADD的敲低（而非RIP 1）可抑制TNFα诱导的caspase途径激活，并随后抑制RIP 3敲低的L929细胞中的细胞凋亡。此外，TRADD在RIP 3非依赖性凋亡过程中结合并激活caspase 8，表明TRADD通过激活caspase途径启动RIP 3非依赖性凋亡。总之，我们确定了RIP 3非依赖性凋亡的靶点和机制，并阐明了RIP 3和TRADD在TNFα刺激后介导L929细胞程序性细胞死亡中的协调作用。
Receptor-interacting protein kinase 3 (RIP3) is a critical initiator in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) in L929 cells, so knockdown of RIP3 inhibits TNFα-induced L929 cell necroptosis. However, RIP3 knockdown was shown to switch TNFα-induced necroptosis to apoptosis in L929 cells in other studies. Therefore, whether RIP3 knockdown blocks the TNFα-induced death of L929 cells is controversial. In this study, TNFα activated caspase pathway and induced cell death in RIP3 knockdown L929 cells, and the RIP3-independent cell death had been blocked by Z-VAD-FMK (pan-caspase inhibitor) or caspase 8 knockdown, demonstrating that RIP3 knockdown switched TNFα-induced necroptosis to caspase-dependent apoptosis. Although both TNF receptor type 1-associated death domain protein (TRADD) and RIP1 have been reported to mediate TNFα-induced apoptosis, the knockdown of TRADD, but not RIP1, suppressed TNFα-induced activation of the caspase pathway and subsequent apoptosis in RIP3 knockdown L929 cells. In addition, TRADD bound and activated caspase 8 during the RIP3-independent apoptosis process, indicating that TRADD initiates RIP3-independent apoptosis by activating the caspase pathway. Collectively, we identified the target and mechanism underlying RIP3-independent apoptosis and elucidated the coordinated roles of RIP3 and TRADD in mediating the programmed cell death of L929 cells following TNFα stimulation.
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影响因子：
64.5
作者：
Micheau, O;Tschopp, J
通讯作者：
Tschopp, J
DOI：
10.1073/pnas.0806585105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Chen, Nien-Jung;Chio, Iok In Christine;Mak, Tak W.
通讯作者：
Mak, Tak W.
影响因子：
12.4
作者：
Kearney, C. J.;Cullen, S. P.;Martin, S. J.
通讯作者：
Martin, S. J.
影响因子：
4.3
作者：
Pobezinskaya, Yelena L.;Liu, Zhenggang
通讯作者：
Liu, Zhenggang
在细胞死亡和炎症的串扰中进行了编程坏死。
影响因子：
29.7
作者：
Chan FK;Luz NF;Moriwaki K
通讯作者：
Moriwaki K