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Science 302 (5650): 1581-1584

Copyright © 2003 by the American Association for the Advancement of Science

Regulation of NF-{kappa}B-Dependent Lymphocyte Activation and Development by Paracaspase

Astrid A. Ruefli-Brasse,1 Dorothy M. French,2 Vishva M. Dixit1*

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 {kappa}B (NF-{kappa}B) activation. We demonstrate that primary T and B lymphocytes from paracaspase-deficient mice are defective in antigen-receptor–induced NF-{kappa}B activation, cytokine production, and proliferation. Paracaspase acts downstream of Bcl10 to induce NF-{kappa}B activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the I{kappa}B kinase complex.

1 Molecular Oncology Department, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
2 Pathology Department, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.

* To whom correspondence should be addressed. E-mail: dixit{at}gene.com

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