MALT1 Protease: A New Therapeutic Target in B Lymphoma and Beyond?

The identification of mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) as a gene that is perturbed in the B-cell neoplasm MALT lymphoma, already more than a decade ago, was the starting point for an intense area of research. The fascination with MALT1 was fueled further by the observation that it contains a domain homologous to the catalytic domain of caspases and thus, potentially, could function as a protease. Discoveries since then initially revealed that MALT1 is a key adaptor molecule in antigen receptor signaling to the transcription factor NF-κB, which is crucial for lymphocyte function. However, recent discoveries show that this function of MALT1 is not restricted to lymphocytes, witnessed by the ever-increasing list of receptors from cells within and outside of the immune system that require MALT1 for NF-κB activation. Yet, a role for MALT1 protease activity was shown only recently in immune signaling, and its importance was then further strengthened by the dependency of NF-κB-addicted B-cell lymphomas on this proteolytic activity. Therapeutic targeting of MALT1 protease activity might, therefore, become a useful approach for the treatment of these lymphomas and, additionally, an effective strategy for treating other neoplastic and inflammatory disorders associated with deregulated NF-κB signaling.