TNFR1诱导的促凋亡信号传导
中文名称
通路描述
肿瘤坏死因子受体1（TNFR1）的激活可触发多种信号转导通路以诱导细胞存活或细胞死亡（Ward C et al. 1999; Micheau O and Tschopp J 2003; Widera D et al. 2006）。虽然促存活信号通过细胞膜上激活的TNFR1受体复合物启动和调节，但TRADD:TRAF2:RIP1复合物从膜释放到细胞质中形成促死亡信号复合物（DISC）时，诱导细胞死亡信号（Micheau O and Tschopp J 2003; Schneider-Brachert W et al. 2004）。在凋亡刺激下，procaspase-8或10被招募到DISC中，密切的邻近促进启动子caspase-8（和/或caspase-10）的二聚化、自催化加工和激活（Wang J et al. 2001; Boatright KM and Salvesen GS 2003）。启动子caspase随后在蛋白酶级联反应中加工和激活下游效应caspase，如caspase-3，最终诱导细胞死亡。
英文描述
TNFR1-induced proapoptotic signaling Activation of tumor necrosis factor receptor 1 (TNFR1) can trigger multiple signal transduction pathways to induce cell survival or cell death (Ward C et al. 1999; Micheau O and Tschopp J 2003; Widera D et al. 2006). While pro-survival signaling is initiated and regulated via the activated TNFR1 receptor complex at the cell membrane, cell death signals are induced upon the release of TRADD:TRAF2:RIP1 complex from the membrane to the cytosol where it forms death-inducing signaling complex (DISC) (Micheau O and Tschopp J 2003; Schneider-Brachert W et al. 2004). Upon apoptotic stimulation procaspase-8 or 10 is recruited into the DISC, and close proximity promotes the dimerization, autocatalytic processing, and activation of the initiator caspase-8 (and/or caspase-10) (Wang J et al. 2001; Boatright KM and Salvesen GS 2003). The initiator caspases then process and activate the downstream effector caspases such as caspase-3 in a proteolytic cascade (Stennicke HR et al. 1998). The effector caspases in turn cleave many diverse substrates, ultimately inducing cell death.
所含基因
26 个基因