Van Nuffel Elien, Schmitt Anja, Afonina Inna S, Schulze-Osthoff Klaus, Beyaert Rudi, Hailfinger Stephan
Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, Ghent University-VIB, Ghent, Belgium; Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
J Invest Dermatol. 2017 Mar;137(3):569-575. doi: 10.1016/j.jid.2016.09.031. Epub 2016 Dec 8.
Mutations in caspase recruitment domain-containing protein 14(CARD14) have been linked to susceptibility to psoriasis. CARD14 is an intracellular scaffold protein that regulates proinflammatory gene expression. Recent studies have offered novel insights into the mechanisms of CARD14-mediated signaling in keratinocytes and the molecular impact of psoriasis-associated CARD14 mutations. CARD14 forms a signaling complex with BCL10 and the paracaspase MALT1, and this process is enhanced upon pathogenic CARD14 mutation, culminating in the activation of MALT1 protease activity and psoriasis-associated gene expression. This review summarizes the current knowledge of CARD14/MALT1-mediated signaling in keratinocytes and its therapeutic implications in psoriasis.
含半胱天冬酶招募结构域蛋白14(CARD14)的突变与银屑病易感性相关。CARD14是一种调节促炎基因表达的细胞内支架蛋白。最近的研究为角质形成细胞中CARD14介导的信号传导机制以及银屑病相关CARD14突变的分子影响提供了新的见解。CARD14与BCL10和副半胱天冬酶MALT1形成信号复合物,并且在致病性CARD14突变时这一过程会增强,最终导致MALT1蛋白酶活性激活和银屑病相关基因表达。本综述总结了目前关于角质形成细胞中CARD14/MALT1介导的信号传导及其在银屑病治疗中的意义的知识。