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The paracaspase MALT 1 mediates CARD 14‐induced signaling in keratinocytes
Author(s) -
Afonina Inna S,
Van Nuffel Elien,
Baudelet Griet,
Driege Yasmine,
Kreike Marja,
Staal Jens,
Beyaert Rudi
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201642109
Subject(s) - signal transduction , microbiology and biotechnology , biology , chemokine , immunology , inflammation
Mutations in CARD 14 have recently been linked to psoriasis susceptibility. CARD 14 is an epidermal regulator of NF ‐κB activation. However, the ability of CARD 14 to activate other signaling pathways as well as the biochemical mechanisms that mediate and regulate its function remain to be determined. Here, we report that in addition to NF ‐κB signaling, CARD 14 activates p38 and JNK MAP kinase pathways, all of which are dependent on the paracaspase MALT 1. Mechanistically, we demonstrate that CARD 14 physically interacts with paracaspase MALT 1 and activates MALT 1 proteolytic activity and inflammatory gene expression, which are enhanced by psoriasis‐associated CARD 14 mutations. Moreover, we show that MALT 1 deficiency or pharmacological inhibition of MALT 1 catalytic activity inhibits pathogenic mutant CARD 14‐induced cytokine and chemokine expression in human primary keratinocytes. Collectively, our findings demonstrate a novel role for MALT 1 in CARD 14‐induced signaling and indicate MALT 1 as a valuable therapeutic target in psoriasis.