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Nat Immunol. 2013 Apr;14(4):337-45. doi: 10.1038/ni.2540. Epub 2013 Feb 17.

The protease activity of the paracaspase MALT1 is controlled by monoubiquitination.

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  • 1Department of Biochemistry, Center of Immunity and Infection, University of Lausanne, Epalinges, Switzerland.

Abstract

The protease activity of the paracaspase MALT1 is central to lymphocyte activation and lymphomagenesis, but how this activity is controlled remains unknown. Here we identify a monoubiquitination of MALT1 on Lys644 that activated the protease function of MALT1. Monoubiquitinated MALT1 had enhanced protease activity, whereas a ubiquitination-deficient MALT1 mutant with replacement of that lysine with arginine (MALT1(K644R)) had less protease activity, which correlated with impaired induction of interleukin 2 (IL-2) via the T cell antigen receptor in activated T cells. Expression of MALT1(K644R) diminished the survival of cells derived from diffuse large B cell lymphoma of the activated B cell-like subtype (ABC DLBCL), which require constitutive protease activity of MALT1 for survival. Thus, monoubiquitination of MALT1 is essential for its catalytic activation and is therefore a potential target for the treatment of ABC-DLBCL and for immunomodulation.

[PubMed - indexed for MEDLINE]
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