Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes
Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes
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DOI：
10.1038/sj.cdd.4401408
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发表时间：
2004-07-01
影响因子：
12.4
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
O'Reilly, LA;Divisekera, U;Strasser, A
衔接蛋白FADD/MORT 1对于由“死亡受体”如Fas（APO-1/CD 95）诱导的细胞凋亡是必需的，介导聚集和caspase-8的自催化活化。也许令人惊讶的是，FADD和半胱天冬酶-8也是有丝分裂原诱导的T淋巴细胞增殖的关键。我们产生了新的单克隆抗体特异性小鼠FADD和caspase-8的细胞反应，细胞凋亡或增殖，是否可以解释这些蛋白质的翻译后修饰和亚细胞定位的差异。在这两个凋亡信号和促有丝分裂激活，FADD和caspase-8聚集在多蛋白复合物，并在质膜上形成帽，但他们没有与脂筏共定位。有趣的是，促有丝分裂刺激，而不是Fas连接，诱导一个独特的翻译后修饰FADD。这些不同的修饰可以决定FADD和半胱天冬酶-8是否诱导细胞死亡或增殖。
The adaptor protein FADD/MORT1 is essential for apoptosis induced by 'death receptors', such as Fas (APO-1/CD95), mediating aggregation and autocatalytic activation of caspase-8. Perhaps surprisingly, FADD and caspase-8 are also critical for mitogen-induced proliferation of T lymphocytes. We generated novel monoclonal antibodies specific for mouse FADD and caspase-8 to investigate whether cellular responses, apoptosis or proliferation, might be explained by differences in post-translational modification and subcellular localisation of these proteins. During both apoptosis signalling and mitogenic activation, FADD and caspase-8 aggregated in multiprotein complexes and formed caps at the plasma membrane but they did not colocalise with lipid rafts. Interestingly, mitogenic stimulation, but not Fas ligation, induced a unique post-translational modification of FADD. These different modifications may determine whether FADD and caspase-8 induce cell death or proliferation.