Targeting B-cell lymphomas with inhibitors of the MALT1 paracaspase
S Hailfinger, G Lenz, M Thome - Current opinion in chemical biology, 2014 - Elsevier
S Hailfinger, G Lenz, M Thome
Current opinion in chemical biology, 2014•ElsevierHighlights•MALT1 is an Arg-specific protease that is activated upon antigen receptor
triggering.•MALT1 cleaves multiple substrates to promote lymphocyte proliferation and
survival.•ABC DLBCL and MALT lymphomas activate MALT1 by specific gene
alterations.•Many mantle cell lymphomas have constitutive BCR signaling and MALT1
activity.•Small molecule MALT1 inhibitors impair growth of xenografted ABC DLBCL.The
paracaspase MALT1 is an Arg-specific protease that cleaves multiple substrates to promote …
triggering.•MALT1 cleaves multiple substrates to promote lymphocyte proliferation and
survival.•ABC DLBCL and MALT lymphomas activate MALT1 by specific gene
alterations.•Many mantle cell lymphomas have constitutive BCR signaling and MALT1
activity.•Small molecule MALT1 inhibitors impair growth of xenografted ABC DLBCL.The
paracaspase MALT1 is an Arg-specific protease that cleaves multiple substrates to promote …
Highlights
- MALT1 is an Arg-specific protease that is activated upon antigen receptor triggering.
- MALT1 cleaves multiple substrates to promote lymphocyte proliferation and survival.
- ABC DLBCL and MALT lymphomas activate MALT1 by specific gene alterations.
- Many mantle cell lymphomas have constitutive BCR signaling and MALT1 activity.
- Small molecule MALT1 inhibitors impair growth of xenografted ABC DLBCL.
The paracaspase MALT1 is an Arg-specific protease that cleaves multiple substrates to promote lymphocyte proliferation and survival. The catalytic activity of MALT1 is normally tightly regulated by antigen receptor triggering, which promotes MALT1 activation by its inducible monoubiquitination-dependent dimerization. Constitutive MALT1 activity is a hallmark of specific subsets of B-cell lymphomas, which are characterized by chromosomal translocations or point mutations that activate MALT1 or its upstream regulators. Recent findings suggest that such lymphomas may be sensitive to treatment with MALT1 inhibitors. Here we review recent progress in the understanding of MALT1 function and regulation, and the development of small molecule MALT1 inhibitors for therapeutic applications.
Elsevier