Mechanisms and consequences of MALT1 scaffolding and proteolytic activity in ABC DLBCL

Prof. Dr. rer. nat. Daniel Krappmann

Helmholtz Zentrum München – German Research Center for Environmental Health GmbH
Institute of Molecular Toxicology and Pharmacology(link is external)
Research Unit Cellular Signal Integration(link is external)

E-Mail(link sends e-mail)


Project Summary

Chronic B-cell receptor signaling activates the MALT1 protease to drive survival of the activated B cell-type of diffuse large B cell lymphomas (ABC DLBCL). Here, we will unravel the MALT1 upstream regulation as well as downstream mechanisms that link MALT1 to proliferation and survival of lymphoma cells. More precisely, we will elucidate the function of MALT1 phosphorylation sites in ABC DLBCL that we have recently identified. Further, MALT1 restricts posttranscriptional gene regulation in an acute immune response. We will determine the functional relevance and consequences of MALT1-catalyzed cleavage of RNA regulators Regnase-1 and Roquin in DLBCL.

A small molecule has entered a novel clinical trial for cancer immunotherapy. The molecule inhibits an enzyme called MALT1 that plays a critical role in suppressing immune reactions against tumor cells. Preclinical studies showed that blocking MALT1 activity results in immune reactivation and boosts an anti-tumor immune response.