Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
Cell Adh Migr. 2010 Apr-Jun;4(2):166-8. doi: 10.4161/cam.4.2.11368. Epub 2010 Apr 29.
Cellular DNA undergoes constant assault from a wide range of genotoxic stress. In order to maintain genome integrity, cells develop a repertoire of sophisticated systems to detect DNA damage and mediate cellular responses to DNA damage. Defects in the DNA damage response have been implicated in a variety of disorders including aging and cancer. Tumor suppressor p53 is a key intermediate in DNA damage response by inducing cell cycle arrest to allow repair or promoting apoptosis to eliminate irreparably damaged cells. A recent study described a novel layer of p53-mediated cellular response to DNA damage, i.e., modulation of cell adhesion and motility. JMY, a p53 co-factor, was demonstrated to be a multifunctional protein that coordinates cell adhesion and motility with nuclear p53 response. These results suggest that abnormal JMY activity and/or localization could contribute to tumor invasion and reveal JMY as a potential therapeutic target.
细胞 DNA 会不断受到各种遗传毒性应激的攻击。为了维持基因组完整性，细胞发展出了一系列复杂的系统来检测 DNA 损伤，并介导细胞对 DNA 损伤的反应。DNA 损伤反应的缺陷与多种疾病有关，包括衰老和癌症。肿瘤抑制因子 p53 是 DNA 损伤反应的关键中间物，它通过诱导细胞周期停滞来允许修复，或促进细胞凋亡来消除无法修复的受损细胞。最近的一项研究描述了 p53 介导的细胞对 DNA 损伤的一种新的反应层，即调节细胞黏附和运动。JMY，p53 的共因子，被证明是一种多功能蛋白，它与核 p53 反应协调细胞黏附和运动。这些结果表明，异常的 JMY 活性和/或定位可能导致肿瘤侵袭，并揭示 JMY 作为一个潜在的治疗靶点。
