Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705, Republic of Korea.
Biochem Biophys Res Commun. 2011 Apr 29;408(1):149-53. doi: 10.1016/j.bbrc.2011.03.139. Epub 2011 Apr 5.
The mutant K-Ras elevates intracellular reactive oxygen species (ROS) levels and leads to oxidative DNA damage, resulting in malignant cell transformation. Ras association domain family 1 isoform A (RASSF1A) is known to play a role as a Ras effector. However, the suppressive effect of RASSF1A on K-RasV12-induced ROS increase and DNA damage has not been identified. Here, we show that RASSF1A blocks K-RasV12-triggered ROS production. RASSF1A expression also inhibits oxidative DNA damage and chromosomal damage. From the results obtained in this study, we suggest that RASSF1A regulates the cellular ROS levels enhanced by the Ras signaling pathway, and that it may function as a tumor suppressor by suppressing DNA damage caused by activated Ras.
突变型 K-Ras 会提高细胞内的活性氧（ROS）水平，并导致氧化 DNA 损伤，从而导致恶性细胞转化。Ras 相关结构域家族 1 亚型 A（RASSF1A）已知作为 Ras 效应物发挥作用。然而，RASSF1A 对 K-RasV12 诱导的 ROS 增加和 DNA 损伤的抑制作用尚未确定。在这里，我们表明 RASSF1A 阻止了 K-RasV12 触发的 ROS 产生。RASSF1A 的表达还抑制了氧化 DNA 损伤和染色体损伤。根据本研究的结果，我们认为 RASSF1A 调节 Ras 信号通路增强的细胞内 ROS 水平，并且它可能通过抑制激活的 Ras 引起的 DNA 损伤而作为肿瘤抑制因子发挥作用。
