Lam Brian, Roudier Emilie
Angiogenesis Research Group, School of Kinesiology and Health Sciences, Muscle Health Research Center, Faculty of Health, York University, Toronto, ON, Canada.
Front Cell Dev Biol. 2019 Dec 10;7:320. doi: 10.3389/fcell.2019.00320. eCollection 2019.
The E3 ubiquitin ligase Murine double minute 2 (MDM2) is the main negative regulator of the tumor protein p53 (TP53). Extensive studies over more than two decades have confirmed MDM2 oncogenic role through mechanisms both TP53-dependent and TP53-independent oncogenic function. These studies have contributed to designate MDM2 as a therapeutic target of choice for cancer treatment and the number of patents for MDM2 antagonists has increased immensely over the last years. However, the question of the physiological functions of MDM2 has not been fully resolved yet, particularly when expressed and regulated physiologically in healthy tissue. Cardiovascular complications are almost an inescapable side-effect of anti-cancer therapies. While several MDM2 antagonists are entering phase I, II and even III of clinical trials, this review proposes to bring awareness on the physiological role of MDM2 in the cardiovascular system.
E3泛素连接酶小鼠双微体2（MDM2）是肿瘤蛋白p53（TP53）的主要负调控因子。二十多年来的广泛研究通过TP53依赖和TP53非依赖的致癌功能机制证实了MDM2的致癌作用。这些研究促使将MDM2指定为癌症治疗的首选治疗靶点，并且在过去几年中，MDM2拮抗剂的专利数量大幅增加。然而，MDM2的生理功能问题尚未完全解决，特别是在健康组织中生理表达和调节时。心血管并发症几乎是抗癌治疗不可避免的副作用。虽然几种MDM2拮抗剂正在进入临床试验的I期、II期甚至III期，但本综述建议提高对MDM2在心血管系统中生理作用的认识。
