Review Article Delineating Molecular Mechanisms of Squamous Tissue Homeostasis and Neoplasia: Focus on p63

Copyright © 2013 Kathryn E. King et al.This is an open access article distributed under theCreativeCommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mouse models have informed us that p63 is critical for normal epidermal development and homeostasis. The p53/p63/p73 family is expressed as multiple protein isoforms due to a combination of alternative promoter usage and C-terminal alternative splicing. These isoforms can mimic or interfere with one another, and their balance ultimately determines biological outcome in a context-dependentmanner.While not frequentlymutated, p63, and in particular theΔNp63 subclass, is commonly overexpressed in human squamous cell cancers. In vitro keratinocytes andmurine transgenic and transplantationmodels have been invaluable in elucidating the contribution of altered p63 levels to cancer development, and studies have identified the roles forΔNp63 isoforms in keratinocyte survival and malignant progression, likely due in part to their transcriptional regulatory function. These findings can be extended to human cancers; for example, the novel recognition of N