Control of immune homeostasis and activation by MALT1-TRAF6 interaction

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MALT1 (Mucosa associated lymphoid tissue protein 1) functions as a key regulator of immunity. As a subunit of the CBM (CARD11-BCL10-MALT1) signalosome, MALT1 channels upstream T and B cell antigen receptor (TCR/BCR) signaling to downstream lymphocyte effector functions. Within the CBM complex, MALT1 has a dual role. As a molecular scaffold, MALT1 initiates NF-κB and JNK signaling. In parallel, MALT1 is a protease and its paracaspase activity modulates immune cell functions by catalyzing the cleavage of substrates involved in signaling, adhesion, transcription and mRNA metabolism. We have previously shown that recruitment of the E3 ligase TRAF6 to MALT1 is driving immune activation, but TRAF6 is also critical for homeostatic control of MALT1 protease to prevent autoimmune inflammation. Alternative splicing of MALT1 controls the binding to TRAF6 and by generating mice carrying the mutation MALT1 E814D, whose ortholog in humans causes a complex immune disorder, we demonstrate that MALT1 splicing and graded TRAF6-MALT1 interaction balances immune homeostasis versus activation. Further, it will be discussed how MALT1-TRAF6 interaction controls adaptive and innate immune responses in a cell-type specific manner and how cleavage of specific MALT1 substrates contribute to loss of immune homeostasis in the absence of TRAF6.


From 20 Mar 2025 13:30
Until 20 Mar 2025 14:30
Location FSVMI building, seminar room

Speaker Daniel Krappmann
Affiliation Research Unit Signaling and Translation, Molecular Targets and Therapeutics Center, Helmholtz Zentrum Münich, German Research Center for Environmental Health, Neuherberg, Germany
Host Rudi Beyaert

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Stream ID 847 6068 6292
Stream Password 759958

About the speaker

Daniel Krappmann started his academic career as a PhD student and continued his studies on signal transduction in cancer cells as a postdoctoral fellow and junior group leader at the Max-Delbrück-Center (MDC) for Molecular Medicine in Berlin. In 2005 he started his group at the Helmholtz Munich, which is dedicated to study physiological and pathological signaling pathways in the immune system and in cancer. Since 2023 he also acts as Director of Research Unit Signaling and Translation.

The identification of the pro-proliferative and anti-apoptotic function of signaling networks in human tumor cells inspired his long-standing efforts to bridge the gap between basic science and clinical translation. He has been leading a successful drug discovery program and the pre-clinical development of new immune modulatory drugs. Candidate drugs from this program are currently tested in the clinic for their ability to boost our immune defence to fight cancer.

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Seminar