Protein kinases coordinately regulate the p53:ΔNp63α axis after DNA damage

Abstract

The ancestral member of the p53 gene family, p63, is overexpressed in head and neck squamous cell carcinomas (HNSCC). To date little is known about the regulation of the N-terminal truncated isoform of p63 (ΔNp63α) which is considered a marker of certain epithelial stem cells and cancer stem cells. In this issue of Cell Cycle, a study (Huang et al.) provides insight into the DNA-damage induced post-translational regulation of ΔNp63α protein stability by the ATM pathway. The data imply that ATM has evolved to act as a master regulator in the basal skin stem cell to co-ordinately switch off ΔNp63α and switch on p53 after irradiation. This would attenuate the proliferative capacity of the stem cell in order for DNA damage to be repaired by the p53 response. These data also have implications for how inactivation of the ATM pathway could promote carcinogenesis in squamous cancers via upregulation of ΔNp63α and for developing novel therapeutic strategies for inhibiting ΔNp63α in cancer stem cell populations.

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