Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University, Cheongju 28644, Republic of Korea.
Department of Thoracic and Cardiovascular Surgery, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea.
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 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.
细胞周期是细胞生长和分裂过程中发生的一系列事件。在细胞周期的 G 期，细胞监测其对特定信号的累积暴露，并做出通过限制（R）点的关键决策。R 点决策机制对于正常分化、细胞凋亡和 G1-S 期转换至关重要。该机制的失调与肿瘤发生明显相关。因此，鉴定控制 R 点决策的分子机制是肿瘤生物学的基本问题之一。 是肿瘤中经常因表观遗传改变而失活的基因之一。特别是在大多数 激活的人类和小鼠肺腺癌（ADC）中，下调。在小鼠肺中靶向失活 会诱导腺瘤（AD），并显著缩短致癌 诱导的 ADC 形成的潜伏期。RUNX3 参与 R 点相关激活剂（RPA-RX3-AC）复合物的瞬时形成，该复合物可测量 RAS 信号的持续时间，从而保护细胞免受致癌 RAS 的影响。本文综述了 R 点参与致癌监测的分子机制。
