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Regulation of MYC by CARD14 in Human Epithelium is a Determinant of Epidermal Homeostasis and Disease II

GSE263428 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/07/13 Platform GPL30173
Summary
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 NFκB, however, CARD14-NFκB signaling does not fully explain the heterogeneity of CARD14-driven disease. Herein, 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 a 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 NFκB 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.
Published in
Regulation of MYC by CARD14 in human epithelium is a determinant of epidermal homeostasis and disease
DeVore SB, Schuetz M, Alvey L et al. · Cell reports 2024 · PMID 39110589 · doi:10.1016/j.celrep.2024.114589
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Also filed as BioProject PRJNA1097530 and SRA study SRP500291. Searching any of these in the dataset finder brings you back here.

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