Rabbit Anti-Human MALT1 polyclonal antibody

CARMA proteins represent a family of scaffold molecules which play several crucial biological functions, including regulation of immune response and inflammation, tissue homeostasis, and modulation of G-Protein Coupled Receptor ( GPCR) signaling. Among the CARMA proteins, CARD14/CARMA2 and its alternatively spliced isoforms are specifically expressed in epithelial cells and keratinocytes. Recent evidences have shown that CARD14/CARMA2 mediates induction of inflammatory response in keratinocytes, and that mutations in CARD14/CARMA2 gene segregate with familial transmission of chronic inflammatory disorders of the human skin. Similarly to CARD11/CARMA1 and CARD10/CARMA3, CARD14/CARMA2 signaling occurs trough formation of a trimeric complex which includes BCL10 and MALT1 proteins. However, it is becoming increasingly evident that in addition to the CBM complex components, a number of accessory molecules are able to finely modulate the signals conveyed on and amplified by CARD14/CARMA2. The study of these molecules is important both to understand the molecular mechanisms that underlie the role of CARMA2 in keratinocytes and because they represent potential therapeutic targets for the development of therapeutic strategies aiming at the treatment of inflammatory diseases of the human skin. In this review, we provide an overview on the molecular mechanisms mediating CARD14/CARMA2 signaling and its implication in our understanding of the pathogenesis of human inflammatory skin disorders.

Background: The paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is crucial for lymphocyte activation through signaling to the transcription factor NF-kappa B. Besides functioning as a scaffold signaling protein, MALT1 also acts as a cysteine protease that specifically cleaves a number of substrates and contributes to specific T cell receptor-induced gene expression. Recently, small molecule inhibitors of MALT1 proteolytic activity were identified and shown to have promising anticancer properties in subtypes of B cell lymphoma. However, information on the therapeutic potential of small compound inhibitors that target MALT1 protease activity in autoimmunity is still lacking. Methods: The present study aimed to elucidate whether MALT1 protease inhibitors are also useful in the treatment of lymphocyte-mediated autoimmune pathologies such as multiple sclerosis (MS). For this, we studied the therapeutic potential of a recently identified inhibitor of MALT1 protease activity, the phenothiazine derivative mepazine, in the context of experimental autoimmune encephalomyelitis (EAE), the main animal model for MS. Results: We demonstrate that administration of mepazine prophylactically or after disease onset, can attenuate EAE. Importantly, while complete absence of MALT1 affects the differentiation of regulatory T (Treg) cells in vivo, the MALT1 protease inhibitor mepazine did not affect Treg development. Conclusions: Altogether, these data indicate that small molecule inhibitors of MALT1 not only hold great promise for the treatment of B cell lymphomas but also for autoimmune disorders such as MS.