Transcriptional programs regulated by p63 in normal epithelium and tumors

The transcription factor p63 belongs to a family of regulatory proteins that bind DNA in a sequence-specific manner, close to a target gene, to activate or repress its transcription. These proteins display a striking conservation of functional domains, but are differentially involved in regulating cellular processes. Nearly a decade after the discovery of p63, its critical role for proper epithelial development, maintenance and tumorigenesis is widely recognized. Several important cellular endpoints have been linked to p63 regulation in epithelium, including differentiation, cell fate specification, proliferation, survival, senescence, apoptosis, cell-cell and cell-matrix interaction programs. Although a large number of genes have been associated with p63-dependent regulation, only a few of these have been validated as direct p63 transcriptional targets. The challenge still remains to define the p63 transcriptome in epithelial cells, and to dissect the cellular mechanisms used to modulate the expression of this transcriptional profile. In this article we will review current knowledge regarding the basic mechanisms used by p63 to regulate gene expression. Also, we will discuss specific p63-regulated biological endpoints in epithelial cells and the specific genes that have been linked to p63 regulation in these particular contexts.