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CARMA Proteins: Playing a Hand of Four CARDs

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Front. Immunol. | doi: 10.3389/fimmu.2018.02167

CARD14/CARMA2 signaling and its role in inflammatory skin disorders

Tiziana Zotti1, Immacolata Polvere1, Serena Voccola1,  Pasquale Vito1* and Romania Stilo1
  • 1University of Sannio, Italy

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.

Keywords: CARD14, CARMA2, NF-kappa B, Psoriasis, Bcl10, Malt1, CBM complex

Received: 06 Jun 2018; Accepted: 03 Sep 2018.

Edited by:

Andrew L. Snow, Uniformed Services University of the Health Sciences, United States

Reviewed by:

Jolan E. Walter, University of South Florida, United States
Levi Watkin, Baylor College of Medicine, United States  

Copyright: © 2018 Zotti, Polvere, Voccola, Vito and Stilo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Pasquale Vito, University of Sannio, Benevento, Italy,