Publication Date:
2005-03-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Helen -- Bidere, Nicolas -- Zheng, Lixin -- Cubre, Alan -- Sakai, Keiko -- Dale, Janet -- Salmena, Leonardo -- Hakem, Razqallah -- Straus, Stephen -- Lenardo, Michael -- New York, N.Y. -- Science. 2005 Mar 4;307(5714):1465-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15746428" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Chloromethyl Ketones/pharmacology
;
Animals
;
Apoptosis
;
B-Lymphocytes/immunology/metabolism
;
Caspase 8
;
Caspases/genetics/*metabolism
;
Cell Line
;
Cell Nucleus/metabolism
;
Cysteine Proteinase Inhibitors/pharmacology
;
Humans
;
I-kappa B Kinase
;
Immunity, Innate
;
Immunologic Deficiency Syndromes/immunology/metabolism
;
Isoenzymes/metabolism
;
Killer Cells, Natural/immunology/metabolism
;
Lipopolysaccharides/immunology
;
Lymphocyte Activation
;
Membrane Glycoproteins/metabolism
;
Mice
;
Mutation
;
NF-kappa B/*metabolism
;
Phosphorylation
;
Protein Kinase C/metabolism
;
Protein-Serine-Threonine Kinases/metabolism
;
Receptors, Antigen, T-Cell/*immunology
;
Receptors, Cell Surface/metabolism
;
Receptors, IgG/immunology
;
Signal Transduction
;
T-Lymphocytes/immunology/metabolism
;
Toll-Like Receptor 4
;
Toll-Like Receptors
;
Transcription Factor RelA
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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