MALT1 paracaspase: a unique protease involved in B-cell lymphomagenesis

Abstract

SUMMARY MALT1 is a key regulator of adaptive immunity. MALT1-dependent signaling events control survival, proliferation and differentiation of lymphocytes in response to T- or B-cell receptor stimulation. MALT1 not only regulates physiological lymphocyte activation, but also controls oncogenic signaling in distinct lymphoid malignancies. The fusion protein API2–MALT1 generated by the chromosomal translocation t(11;18) acts as an oncoprotein in the late stages of mucosa-associated lymphoid tissue lymphoma. Moreover, MALT1 is critical for survival and proliferation of the activated B-cell type of diffuse large B-cell lymphomas, one of the most aggressive entities of malignant lymphomas. On the molecular level, MALT1 serves a dual role by functioning as a signaling adaptor and a protease. Both of these functions are critical for triggering the adaptive immune response and for promoting lymphomagenesis. Recent data emphasize that MALT1 is a promising drug target for the treatment of aggressive lymphomas.