Requirement for caspase-8 in NF-κB activation by antigen receptor
Requirement for caspase-8 in NF-κB activation by antigen receptor
复制标题
DOI：
10.1126/science.1104765
复制
发表时间：
2005-03-04
期刊：
影响因子：
56.9
通讯作者：
Lenardo, M
中科院分区：
文献类型：
--
作者：
Su, H;Bidère, N;Lenardo, M
Caspase-8是一种促凋亡蛋白酶，在淋巴细胞活化和保护性免疫中起重要作用。我们发现，caspase-8缺陷（CED）在人类和小鼠中特异性地消除了通过抗原受体、Fc受体或T、B和自然杀伤细胞中的Toll样受体4刺激后转录因子核因子κ B（NF-κ B）的激活。半胱天冬酶-8还导致NF-κ B激酶抑制剂（IKK）的上游复合物与上游Bcl 10-MALT 1（粘膜相关淋巴组织）衔接复合物结合。IKK α、β复合物的募集、激活和NF-κ B的核转位需要全长caspase-8的酶活性。因此，这些发现解释了人类CED中缺陷性细胞凋亡和联合免疫缺陷的矛盾关联。
Caspase-8, a proapoptotic protease, has an essential role in lymphocyte activation and protective immunity. We show that caspase-8 deficiency (CED) in humans and mice specifically abolishes activation of the transcription factor nuclear factor kappaB (NF-kappaB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. Caspase-8 also causes the up complex of the inhibitor of NF-kappaB kinase (IKK) to associate with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex. Recruitment of the IKKalpha,beta complex, its activation, and the nuclear translocation of NF-kappaB require enzyme activity of full-length caspase-8. These findings thus explain the paradoxical association of defective apoptosis and combined immunodeficiency in human CED.