Role of RUNX3 in Restriction Point Regulation.

A cell cycle is a series of events that takes place in a cell as it grows and divides. At the G phase of cell cycle, cells monitor their cumulative exposure to specific signals and make the critical decision to pass through the restriction (R)-point. The R-point decision-making machinery is fundamental to normal differentiation, apoptosis, and G-S transition. Deregulation of this machinery is markedly associated with tumorigenesis. Therefore, identification of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in tumor biology. is one of the genes frequently inactivated in tumors by epigenetic alterations. In particular, is downregulated in most -activated human and mouse lung adenocarcinomas (ADCs). Targeted inactivation of in the mouse lung induces adenomas (ADs), and markedly shortens the latency of ADC formation induced by oncogenic . RUNX3 participates in the transient formation of R-point-associated activator (RPA-RX3-AC) complexes, which measure the duration of RAS signals and thereby protect cells against oncogenic RAS. This review focuses on the molecular mechanism by which the R-point participates in oncogenic surveillance.