Figure 1. p63 is the primordial member of the p53/p63/p73 family of transcription factors.

The human TP63 gene consists of 15 exons spanning ~270 kb and maps to chromosome 3q27 [3]. It encodes two classes of isoforms generated by alternative promoters: TAp63 transcripts, which possess an N-terminal transactivation domain, and ΔNp63 isoforms that lack the N-terminal transactivation domain but retain the ability to induce genes via a second transcription activation domain. Alternative splicing occurring at the 3’ end of p63 mRNAs generates multiple C-terminal variants (α, β, γ, δ and ε) for both TAp63 and ΔNp63 classes [3]. TAp63- and ΔNp63- isoforms have distinct tissue distributions. ΔNp63 but not TAp63 is present in basal and parabasal cells in squamous epithelium and urinary bladder, and in basal cells of breast and prostate. TAp63 is detected in lymphocytes and germ cell precursors and some mesenchymal cells and endothelial cells. The existence of multiple isoforms of TP63 with differing functions allows TP63 to regulate a wide array of biological processes such as development and differentiation, senescence, proliferation, stem cell maintenance, and apoptosis [4]. In the context of cancer, TAp63 isoforms are generally regarded as tumor suppressors, [4]. However, ΔNp63 isoforms—ΔNp63α in particular—frequently act as oncogenes.