Role of RUNX3 in Restriction Point Regulation

Cells. 2023 Feb 23;12(5):708. doi: 10.3390/cells12050708.


A cell cycle is a series of events that takes place in a cell as it grows and divides. At the G1 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 G1-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. RUNX3 is one of the genes frequently inactivated in tumors by epigenetic alterations. In particular, RUNX3 is downregulated in most K-RAS-activated human and mouse lung adenocarcinomas (ADCs). Targeted inactivation of Runx3 in the mouse lung induces adenomas (ADs), and markedly shortens the latency of ADC formation induced by oncogenic K-Ras. 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.

Keywords: K-RAS; R-point; RUNX3; cell cycle.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung*
  • Adenocarcinoma*
  • Animals
  • Cell Transformation, Neoplastic
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Humans
  • Lung Neoplasms* / genetics
  • Mice


  • Core Binding Factor Alpha 3 Subunit
  • Runx3 protein, human

Grant support

S.-C.B. is supported by a Creative Research Grant (NRF-2014R1A3A2030690) and Medical Research Center (MRC-2020R1A5A2017476) through the National Research Foundation (NRF) of Korea. J.-W.L. is supported by Basic Science Research Program grant (NRF-2021R1I1A1A01060610) of Korea. M.-K.K. is supported by Basic Science Research Program grant (NRF-2017R1A6A3A11028050) of Korea. D.-H.K. is supported by Basic Science Research Program grant (NRF-2020R1F1A1060630).