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Clin Cancer Res. 2013 Dec 15;19(24):6662-8. doi: 10.1158/1078-0432.CCR-12-3869. Epub 2013 Sep 4.

Molecular pathways: targeting MALT1 paracaspase activity in lymphoma.

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Authors' Affiliations: Departments of Medicine and Pharmacology, Weill Cornell Medical College, New York, New York.

Abstract

MALT1 mediates the activation of NF-κB in response to antigen receptor signaling. MALT1, in association with BCL10 and CARD11, functions as a scaffolding protein to activate the inhibitor of IκB kinase (IKK) complex. In addition, MALT1 is a paracaspase that targets key proteins in a feedback loop mediating termination of the NF-κB response, thus promoting activation of NF-κB signaling. Activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL), which tend to be more resistant to chemotherapy, are often biologically dependent on MALT1 activity. Newly developed MALT1 small-molecule inhibitors suppress the growth of ABC-DLBCLs in vitro and in vivo. This review highlights the recent advances in the normal and disease-related functions of MALT1. Furthermore, recent progress targeting MALT1 proteolytic activity raises the possibility of deploying MALT1 inhibitors for the treatment of B-cell lymphomas and perhaps autoimmune diseases that involve increased B- or T-cell receptor signaling.

PMID:
24004675
DOI:
10.1158/1078-0432.CCR-12-3869
[Indexed for MEDLINE]
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