Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase.
Paracaspase (MALT1), a member of an evolutionarily conserved superfamily of caspase-like proteins, has been shown to bind and colocalize with the protein Bcl10 in vitro and, because of this association, has been suggested to be involved in the CARMA1-Bcl10 pathway of antigen-induced nuclear factor kappaB (NF-kappaB) activation. We demonstrate that primary T and B lymphocytes from paracaspase-deficient mice are defective in antigen-receptor-induced NF-kappaB activation, cytokine production, and proliferation. Paracaspase acts downstream of Bcl10 to induce NF-kappaB activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the IkappaB kinase complex.
Molecular Oncology Department, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Astrid A
AA
Ruefli-Brasse
Dorothy M
DM
French
Vishva M
VM
Dixit
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis; D000074018:B-Cell CLL-Lymphoma 10 Protein; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D020169:Caspases; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D017353:Gene Deletion; D018390:Gene Targeting; D051528:Guanylate Kinases; D051550:I-kappa B Kinase; D008213:Lymphocyte Activation; D018442:Lymphoma, B-Cell, Marginal Zone / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C488088:Bcl10 protein, mouse; D016207:Cytokines; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; D020169:Caspases; C498509:Malt1 protein, mouse; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein