O'Brate Aurora, Giannakakou Paraskevi
Winship Cancer Institute, Emory University, 1365-C Clifton Road, N.E., Room C4078, Atlanta, GA 30322, USA.
Drug Resist Updat. 2003 Dec;6(6):313-22. doi: 10.1016/j.drup.2003.10.004.
The regulation of p53 functions is tightly controlled through several mechanisms including p53 transcription and translation, protein stability, post-translational modifications, and subcellular localization. Despite intensive study of p53, the regulation of p53 subcellular localization although important for its function is still poorly understood. The regulation of p53 localization depends on factors that influence its nuclear import and export, subnuclear localization and cytoplasmic tethering and sequestration. In this review, we will focus on various proteins and modifications that regulate the location and therefore the activity of p53. For example, MDM2 is the most important regulator of p53 nuclear export and degradation. Cytoplasmic p53 associates with the microtubule cytoskeleton and the dynein family of motor proteins; while Parc and mot2 are involved in its cytoplasmic sequestration. Finally, a portion of p53 is localized to the mitochondria as part of the non-transcriptional apoptotic response. In this review we strive to present the most recent data on how the activity of p53 is regulated by its location.
p53功能的调控通过多种机制严格控制，包括p53的转录和翻译、蛋白质稳定性、翻译后修饰以及亚细胞定位。尽管对p53进行了深入研究，但p53亚细胞定位的调控虽然对其功能很重要，但仍了解甚少。p53定位的调控取决于影响其核输入和输出、核内亚定位以及细胞质锚定和隔离的因素。在本综述中，我们将重点关注调节p53定位从而调控其活性的各种蛋白质和修饰。例如，MDM2是p53核输出和降解的最重要调节因子。细胞质中的p53与微管细胞骨架和动力蛋白的动力蛋白家族相关联；而Parc和mot2则参与其细胞质隔离。最后，一部分p53作为非转录凋亡反应的一部分定位于线粒体。在本综述中，我们努力呈现关于p53活性如何受其定位调控的最新数据。
