抗原受体激活NF-κB过程中半胱天冬酶-8的需求

Requirement for caspase-8 in NF-kappaB activation by antigen receptor.

作者信息

Su Helen, Bidère Nicolas, Zheng Lixin, Cubre Alan, Sakai Keiko, Dale Janet, Salmena Leonardo, Hakem Razqallah, Straus Stephen, Lenardo Michael

机构信息

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Science. 2005 Mar 4;307(5714):1465-8. doi: 10.1126/science.1104765.

DOI:10.1126/science.1104765

PMID:15746428

Abstract

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 alphabeta 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.

摘要

半胱天冬酶 -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，人类和小鼠中的半胱天冬酶 -8缺陷（CED）特异性地消除了T细胞、B细胞和自然杀伤细胞通过抗原受体、Fc受体或Toll样受体4刺激后转录因子核因子κB（NF-κB）的活化。半胱天冬酶 -8还导致NF-κB激酶（IKK）的αβ复合物与上游Bcl10-MALT1（黏膜相关淋巴组织）衔接复合物结合。IKKα、β复合物的募集、其活化以及NF-κB的核转位需要全长半胱天冬酶 -8的酶活性。因此，这些发现解释了人类CED中凋亡缺陷与联合免疫缺陷的矛盾关联。