P63 and P73: Teammates or adversaries?

The status and interrelationship of p53 family members are critical elements in tumor progression. An intriguing paper in this issue of Cancer Cell (Rocco et al., 2006) reveals a new twist in the interactions between p63 and p73 following DNA damage, underscoring a role for p73 in the proapoptotic regulation of Puma, Noxa, and Bcl-2 in head and neck squamous cell carcinomas (HNSCC). These data define a pathway in which ΔNp63α promotes survival in squamous epithelial malignancy by repressing a p73-dependent proapoptotic transcriptional program, suggesting that p63 levels and p73 status may be key determinants of tumor response in patients with HNSCC.