Abe Jun-Ichi, Sandhu Uday G, Hoang Nguyet Minh, Thangam Manoj, Quintana-Quezada Raymundo A, Fujiwara Keigi, Le Nhat Tu
Department of Cardiology - Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 2121 W. Holcombe Blvd, Unit Number: 1101, Room Number: IBT8.803E, Houston, TX, 77030, USA.
Adv Exp Med Biol. 2017;963:337-358. doi: 10.1007/978-3-319-50044-7_20.
Sumoylation, a reversible post-transcriptional modification process, of proteins are involved in cellular differentiation, growth, and even motility by regulating various protein functions. Sumoylation is not limited to cytosolic proteins as recent evidence shows that nuclear proteins, those associated with membranes, and mitochondrial proteins are also sumoylated. Moreover, it is now known that sumoylation plays an important role in the process of major human ailments such as malignant, cardiovascular and neurological diseases. In this chapter, we will highlight and discuss how the localization of SUMO protease and SUMO E3 ligase in different compartments within a cell regulates biological processes that depend on sumoylation. First, we will discuss the key role of sumoylation in the nucleus, which leads to the development of endothelial dysfunction and atherosclerosis . We will then discuss how sumoylation of plasma membrane potassium channel proteins are involved in epilepsy and arrhythmia. Mitochondrial proteins are known to be also sumoylated, and the importance of dynamic-related protein 1 (DRP1) sumoylation on mitochondrial function will be discussed. As we will emphasize throughout this review, sumoylation plays crucial roles in different cellular compartments, which is coordinately regulated by the translocation of various SUMO proteases and SUMO E3 ligase. Comprehensive approach will be necessary to understand the molecular mechanism for efficiently moving around various enzymes that regulate sumoylation within cells.
蛋白质的类泛素化修饰是一种可逆的转录后修饰过程，它通过调节各种蛋白质功能参与细胞分化、生长甚至运动。类泛素化修饰并不局限于胞质蛋白，因为最近的证据表明，核蛋白、与膜相关的蛋白以及线粒体蛋白也会发生类泛素化修饰。此外，现在已知类泛素化修饰在人类主要疾病如恶性肿瘤、心血管疾病和神经疾病的发生过程中起重要作用。在本章中，我们将重点介绍并讨论SUMO蛋白酶和SUMO E3连接酶在细胞内不同区室中的定位如何调节依赖于类泛素化修饰的生物学过程。首先，我们将讨论类泛素化修饰在细胞核中的关键作用，它会导致内皮功能障碍和动脉粥样硬化的发展。然后，我们将讨论质膜钾通道蛋白的类泛素化修饰如何参与癫痫和心律失常。已知线粒体蛋白也会发生类泛素化修饰，我们将讨论动力相关蛋白1（DRP1）的类泛素化修饰对线粒体功能的重要性。正如我们将在本综述中始终强调的那样，类泛素化修饰在不同的细胞区室中发挥着关键作用，这是由各种SUMO蛋白酶和SUMO E3连接酶的转位协同调节的。需要采用综合方法来理解细胞内调节类泛素化修饰的各种酶有效移动的分子机制。
