Tp63 in Oral Development, Neoplasia, and Autoimmunity

The Tp63 gene encodes for multiple isoforms of the p63 transcription factor, a member of the p53 family of proteins. Much like its more famous sibling, the biological role of p63 is quite complex, with wide-ranging effects on development, differentiation, and cellular lineage choices. The crucial function of p63 is epitomized by the striking phenotype of p63 knockout mice. These animals have a profound block in the development of stratified epithelia and aplasia of multiple ectodermal appendages, as well as orofacial clefting and limb defects. Remarkably, a similar spectrum of phenotypic alterations is observed in human syndromes resulting from Tp63 gene mutations. p63 is an important hub in the transcriptional and signaling networks of epithelial cells; thus, it is not surprising that dysregulation of this transcription factor is associated with squamous cell carcinoma. Finally, as a testament to the growing repertoire of p63-associated diseases, autoantibodies to p63 are associated with chronic ulcerati...