Regulation of MYC by CARD14 in human epithelium is a determinant of epidermal homeostasis and disease
- PMID: 39110589
- PMCID: PMC11469028
- DOI: 10.1016/j.celrep.2024.114589
Regulation of MYC by CARD14 in human epithelium is a determinant of epidermal homeostasis and disease
Abstract
Caspase recruitment domain family member 14 (CARD14) and its variants are associated with both atopic dermatitis (AD) and psoriasis, but their mechanistic impact on skin barrier homeostasis is largely unknown. CARD14 is known to signal via NF-κB; however, CARD14-NF-κB signaling does not fully explain the heterogeneity of CARD14-driven disease. Here, we describe a direct interaction between CARD14 and MYC and show that CARD14 signals through MYC in keratinocytes to coordinate skin barrier homeostasis. CARD14 directly binds MYC and influences barrier formation in an MYC-dependent fashion, and this mechanism is undermined by disease-associated CARD14 variants. These studies establish a paradigm that CARD14 activation regulates skin barrier function by two distinct mechanisms, including activating NF-κB to bolster the antimicrobial (chemical) barrier and stimulating MYC to bolster the physical barrier. Finally, we show that CARD14-dependent MYC signaling occurs in other epithelia, expanding the impact of our findings beyond the skin.
Keywords: CARD14; CP: Developmental biology; MYC; allergic disease; atopic dermatitis; atopy; barrier homeostasis; epidermis; epithelium; keratinocyte; skin barrier.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests Aspects of this manuscript have been included in a recent patent filing.
Figures







References
-
- Davidson WF, Leung DYM, Beck LA, Berin CM, Boguniewicz M, Busse WW, Chatila TA, Geha RS, Gern JE, Guttman-Yassky E, et al. (2019). Report from the National Institute of Allergy and Infectious Diseases workshop on “Atopic dermatitis and the atopic march: Mechanisms and interventions.”. J. Allergy Clin. Immunol 143, 894–913. 10.1016/j.jaci.2019.01.003. - DOI - PMC - PubMed
-
- Yazici D, Ogulur I, Kucukkase O, Li M, Rinaldi AO, Pat Y, Wallimann A, Wawrocki S, Celebi Sozener Z, Buyuktiryaki B, et al. (2022). Epithelial barrier hypothesis and the development of allergic and autoimmune diseases. Allergo J. Int 31, 91–102. 10.1007/s40629-022-00211-y. - DOI
-
- Montero-Vilchez T, Segura-Fernández-Nogueras M-V, Pérez-Rodríguez I, Soler-Gongora M, Martinez-Lopez A, Fernández-González A, Molina-Leyva A, and Arias-Santiago S (2021). Skin Barrier Function in Psoriasis and Atopic Dermatitis: Transepidermal Water Loss and Temperature as Useful Tools to Assess Disease Severity. J. Clin. Med 10, 359. 10.3390/jcm10020359. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous