Protease activity of MALT1: a mystery unravelled

The Biochemical Journal
Daniel Kirchhofer, Domagoj Vucic

Abstract

Constitutive NF-κB (nuclear factor κB) activation in B-cell lymphomas relies greatly on the CARMA1 [CARD (caspase recruitment domain)-containing MAGUK (membrane-associated guanylate kinase) 1]-Bcl10-MALT1 (mucosa-associated lymphoid tissue translocation gene 1) signalling complex. Within this protein complex, MALT1 possesses a rather unique enzymatic activity, which allows it to cleave Bcl10, RelB and CYLD, among other substrates. The catalytic activity of MALT1 promotes activation of canonical and non-canonical NF-κB as well as other signalling pathways. However, even after a decade of intense research on MALT1, many mechanistic aspects of its enzymatic activity remain elusive. A recent article by Hachmann, Snipas, van Raam, Cancino, Houlihan, Poreba, Kasperkiewicz, Drag and Salvesen [(2012) Biochem. J. 443, 287-295] provides novel insight into the activation mechanism and the substrate specificity of MALT1. These intriguing findings convincingly demonstrate the importance of MALT1 dimerization for its catalytic activity and pave the way for novel therapeutic approaches that target this crucial regulator of lymphoma survival and proliferation.

References

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Citations

Jan 1, 2013·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Claire LugassyRaymond L Barnhill
Aug 5, 2014·The Journal of Allergy and Clinical Immunology·Stuart E TurveyKlaus Warnatz
Aug 12, 2015·Molecular Immunology·Jian-Hong Shi, Shao-Cong Sun
Jun 25, 2013·Pigment Cell & Melanoma Research·Claire LugassyRaymond L Barnhill

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