MALT1 directs B cell receptor-induced canonical nuclear factor-kappaB signaling selectively to the c-Rel subunit

Nat Immunol. 2007 Sep;8(9):984-91. doi: 10.1038/ni1493. Epub 2007 Jul 29.


NF-kappaB (Rel) transcription factors control physiological and pathological immune cell function. The scaffold proteins Bcl-10 and MALT1 couple antigen-receptor signals to the canonical NF-kappaB pathway and are pivotal in lymphomagenesis. Here we found that Bcl-10 and MALT1 differentially regulated B cell receptor-induced activation of RelA and c-Rel. Bcl-10 was essential for recruitment of the kinase IKK into lipid rafts for the activation of RelA and c-Rel, for blocking apoptosis and for inducing division after B cell receptor ligation. In contrast, MALT1 participated in survival signaling but was not involved in IKK recruitment or activation and was dispensable for RelA induction and proliferation. MALT1 selectively activated c-Rel to control a distinct subprogram. Our results provide mechanistic insights into B cell receptor-induced survival and proliferation signals and demonstrate the selective control of c-Rel in the canonical NF-kappaB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis / physiology
  • B-Cell CLL-Lymphoma 10 Protein
  • Caspases / immunology
  • Caspases / metabolism*
  • Cell Division / physiology
  • Cell Survival / physiology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Immunoblotting
  • Immunoprecipitation
  • Lymphocyte Activation / immunology*
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Transgenic
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins c-rel / metabolism*
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*
  • Transcription Factor RelA / metabolism


  • Adaptor Proteins, Signal Transducing
  • B-Cell CLL-Lymphoma 10 Protein
  • Bcl10 protein, mouse
  • NF-kappa B
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-rel
  • Receptors, Antigen, B-Cell
  • Rela protein, mouse
  • Transcription Factor RelA
  • Caspases
  • Malt1 protein, mouse
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein