Guan Dongyin, Kao Hung-Ying
Department of Biochemistry, School of Medicine, Case Western Reserve University, and Comprehensive Cancer Center of Case Western Reserve University, Cleveland, 10900 Euclid Avenue, Cleveland, OH 44106 USA.
Cell Biosci. 2015 Nov 4;5:60. doi: 10.1186/s13578-015-0051-9. eCollection 2015.
The tumor suppressor protein, promyelocytic leukemia protein (PML), was originally identified in acute promyelocytic leukemia due to a chromosomal translocation between chromosomes 15 and 17. PML is the core component of subnuclear structures called PML nuclear bodies (PML-NBs), which are disrupted in acute promyelocytic leukemia cells. PML plays important roles in cell cycle regulation, survival and apoptosis, and inactivation or down-regulation of PML is frequently found in cancer cells. More than 120 proteins have been experimentally identified to physically associate with PML, and most of them either transiently or constitutively co-localize with PML-NBs. These interactions are associated with many cellular processes, including cell cycle arrest, apoptosis, senescence, transcriptional regulation, DNA repair and intermediary metabolism. Importantly, PML inactivation in cancer cells can occur at the transcriptional-, translational- or post-translational- levels. However, only a few somatic mutations have been found in cancer cells. A better understanding of its regulation and its role in tumor suppression will provide potential therapeutic opportunities. In this review, we discuss the role of PML in multiple tumor suppression pathways and summarize the players and stimuli that control PML protein expression or subcellular distribution.
肿瘤抑制蛋白早幼粒细胞白血病蛋白（PML）最初是在急性早幼粒细胞白血病中由于15号和17号染色体之间的染色体易位而被发现的。PML是称为PML核体（PML-NBs）的亚核结构的核心成分，在急性早幼粒细胞白血病细胞中这些核体会被破坏。PML在细胞周期调控、存活和凋亡中发挥重要作用，并且在癌细胞中经常发现PML的失活或下调。已经通过实验鉴定出120多种蛋白质与PML发生物理相互作用，其中大多数蛋白质要么短暂地要么组成性地与PML核体共定位。这些相互作用与许多细胞过程相关，包括细胞周期停滞、凋亡、衰老、转录调控、DNA修复和中间代谢。重要的是，癌细胞中PML的失活可发生在转录、翻译或翻译后水平。然而，在癌细胞中仅发现了少数体细胞突变。更好地了解其调控及其在肿瘤抑制中的作用将提供潜在的治疗机会。在本综述中，我们讨论了PML在多种肿瘤抑制途径中的作用，并总结了控制PML蛋白表达或亚细胞分布的相关因子和刺激因素。
