Abstract
The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.
Highlights
Laboratory of Molecular Oncology, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA
The p53 family members members function as tetramers through their oligomerization domains, with p63 and p73 function as tetramers through their oligomerization domains, with p63 and p73 preferentially interacting preferentially interacting with one another, rather than with p53, and heterotetramers being the with one another, rather than with p53, and heterotetramers being the preferred configuration [12]
This review provides an overview of the critical role of p63, neck and skin [24,25,26]
Summary
Laboratory of Molecular Oncology, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. ∆Np63α activates or represses transcription by binding to promoters of its target genes and associating
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