Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase |
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Authors: | Ruefli-Brasse Astrid A French Dorothy M Dixit Vishva M |
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Institution: | Molecular Oncology Department, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. |
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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. |
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