Our skin, the body’s largest organ–provides the first line of defense against infections and many other threats to our health. Decades of research has shown that a wide range of diseases can occur, or become worse, when the skin cannot form an effective barrier. Millions of people are affected by eczema, psoriasis and other inflammatory skin disorders. Now, experts in human genetics and asthma research at Cincinnati Children’s report discovering a novel molecular signaling pathway that plays a crucial role in maintaining our skin barrier. It seems that an apoptosis-related protein called CARD14, may directly interact with the famous proto-oncogene c-Myc. The far-reaching findings eventually may lead to new ways to prevent and treat inflammatory skin diseases such as atopic dermatitis (ADE or eczema) and psoriasis.
CARD14 is also called Bcl10-Interacting MAGUK Protein 2 (BIMP2) and Psoriasis Susceptibility 2 (PSOR2) and Carma2. It regulates the activation of NF-kB transcription factor invoved in inflammation. Previous research has focused on the CARD14-NFκB signaling pathway, which is thought to promote psoriatic diseases when elevated and to promote atopic dermatitis when reduced. However, according to the research team, that model does not fully explain the variability in CARD14-driven diseases. This new CARD14-MYC signaling pathway strengthens the link between CARD14 and skin barrier health. Belonging to the MAGUK cellular proteins, members of this family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control.
Its signals regulate the function of c-Myc in the most common type of skin cell. Study co-authors say that CARD14 regulates skin barrier function through two mechanisms: stimulating NFκB to establish an antimicrobial barrier and stimulating MYC to help build a physical barrier. This implicates that c-Myc stuìimulates the synthesis of skin proteins like keratins, desmin, desmocollin-3, elastin, collagen isoforms, filaggrin and others. The study further explores how various mutations in CARD14 can promote different skin diseases, including ADE and psoriasis. Importantly, the study reports that altered CARD14-Myc signaling could affect barrier function and allergic diseases in other tissues, contributing to asthma by affecting airway tissue linings or contributing to eosinophilic esophagitis by affecting the digestive tract.
This newly uncovered pathway may contribute to understands diseases caused by CARD14 mutations, like psoriasis type 2 and pytiriasis rubra pilaris, and also contribute to certain cancers that begin in skin, inner mucosae and other epithelial tissues.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
DeVore SB et al. Cell Reports. 2024 Aug; 43(8):114589.
Schmauch E et al. Sci Adv. 2024 Jul; 10(27):eado2365.
Zhou T et al. J Cutan Med Surg. 2024; 28(2):158-166.
Li N, Tao J et al. Pediatr Dermatol. 2023; 40(4):706-709.