p19 ras Brings a New Twist to the Regulation of p73 by Mdm2

p53 is the most commonly mutated gene in human cancer. It is now known that the p53 family proteins p63 and p73 play important roles in tumor suppression as well as in development. Because p63 and p73 are rarely mutated in human cancer, understanding the signaling pathways that activate p63 and p73 will not only shed light on the developmental processes regulated by p63 and p73 but may also yield insight into ways to harness p63 and p73 activity for cancer therapy. Recent research has shown that an alternative splice form of c-H-ras, called p19ras, is a positive regulator of p73beta through a mechanism that involves the E3 ubiquitin ligase Mdm2. Implications for this previously unidentified means of regulation are discussed in light of tumor suppression and are extended to p53 and p63.