Requirement for Caspase-8 in NF-κB Activation by Antigen Receptor
Open Access
- 4 March 2005
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 307 (5714) , 1465-1468
- https://doi.org/10.1126/science.1104765
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 κB (NF-κB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. Caspase-8 also causes the αβ complex of the inhibitor of NF-κB kinase (IKK) to associate with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex. Recruitment of the IKKα, β complex, its activation, and the nuclear translocation of NF-κB require enzyme activity of full-length caspase-8. These findings thus explain the paradoxical association of defective apoptosis and combined immunodeficiency in human CED.Keywords
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