Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase

Science. 2003 Nov 28;302(5650):1581-4. doi: 10.1126/science.1090769. Epub 2003 Oct 23.

Abstract

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Antibody Formation
  • Antigens, CD / analysis
  • B-Cell CLL-Lymphoma 10 Protein
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / physiology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology
  • Caspases
  • Cell Differentiation
  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Cytokines / metabolism
  • Gene Deletion
  • Gene Targeting
  • Guanylate Kinases
  • I-kappa B Kinase
  • Lymphocyte Activation*
  • Lymphoma, B-Cell, Marginal Zone / chemistry
  • Lymphoma, B-Cell, Marginal Zone / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Nucleoside-Phosphate Kinase / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • B-Cell CLL-Lymphoma 10 Protein
  • BCL10 protein, human
  • Bcl10 protein, mouse
  • Cytokines
  • NF-kappa B
  • Neoplasm Proteins
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Protein Serine-Threonine Kinases
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • Ikbke protein, mouse
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases
  • Caspases
  • Malt1 protein, mouse
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein