FIG. 9.

A model depicting the relationship between the p19^Arf-p53 tumor suppressor pathway and the Rho GTPase signaling module in the regulation of cell proliferation and transformation. In addition to malfunction in checkpoint and apoptosis control, deficiency of p19^Arfand/or p53 may alter transcriptional balance and promote cell growth by upregulating PI 3-kinase and Rho GTPase activities. Mitogenic signals that cause activation of RhoA, Rac1, or Cdc42 could further modulate cell cycle and apoptotic machineries and cooperate with p53 deficiency to promote cell hyperproliferation and transformation.