AP1 Transcription Factors in Epidermal Differentiation and Skin Cancer

Abstract

AP1 (jun/fos) transcription factors (c-jun, junB, junD, c-fos, FosB, Fra-1, and Fra-2) are key regulators of epidermal keratinocyte survival and differentiation and important drivers of cancer development. Understanding the role of these factors in epidermis is complicated by the fact that each protein is expressed, at different levels, in multiple cells layers in differentiating epidermis, and because AP1 transcription factors regulate competing processes (i.e., proliferation, apoptosis, and differentiation). Various in vivo genetic approaches have been used to study these proteins including targeted and conditional knockdown, overexpression, and expression of dominant-negative inactivating AP1 transcription factors in epidermis. Taken together, these studies suggest that individual AP1 transcription factors have different functions in the epidermis and in cancer development and that altering AP1 transcription factor function in the basal versus suprabasal layers differentially influences the epidermal differentiation response and disease and cancer development.

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

“…6f) suggests a compromise of normal epidermal differentiation50. FREAC2 (FOXF2) targets are downregulated across the development sequence (Supplementary Fig.…”

Similar response patterns to topical minoxidil foam 5% in frontal and vertex scalp of men with androgenetic alopecia: a microarray analysis

“…The EDC genes map to chromosome 1q21 and encode the calcium-binding proteins of the S100 family, the small proline rich proteins (SPRRs) and the late cornified envelope (LCE) proteins 27,28 that participate in keratinocyte differentiation. EDC gene expression is regulated by the AP1 family of transcription factors (jun/fos) which are major regulators of epidermal differentiation 29 . In addition to EDC genes, a number of inflammatory genes were also down regulated in both the vertex and frontal scalp of AGA patients after minoxidil treatment.…”

Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2

“…Deregulated AP-1 expression is found in skin biopsies of patients with inflammatory/proliferative skin diseases, such as psoriasis, and epithelial cancers, such as squamous cell carcinomas (SCCs) (Zenz et al 2005;Guinea-Viniegra et al 2012Briso et al 2013;Eckert et al 2013). The generation of genetically engineered mouse models (GEMMs) has provided insights into the important functions of Jun proteins as well as c-Fos in epidermal homeostasis, inflammation, and cancer (Zenz et al 2003;Meixner et al 2008;Guinea-Viniegra et al 2009, 2012Bakiri et al 2011;Briso et al 2013;Schonthaler et al 2013).…”