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蛋白磷酸酶 2A 在各种疾病模型中的治疗靶点。

Protein phosphatase 2A as therapeutic targets in various disease models.

机构信息

National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

Toxicology and Biomedicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam.

出版信息

Life Sci. 2018 Oct 1;210:40-46. doi: 10.1016/j.lfs.2018.08.063. Epub 2018 Aug 28.

Abstract

There are a large number of signalling pathways responsible for transmitting information within the cell. Although cellular signalling is thought to be majorly governed by protein kinases 'cascade effects'; their antagonists protein phosphatases also play a crucial dual role in signal transduction. By dephosphorylating the proteins involved in signalling pathways, phosphatases may lead to their activation and sometimes they may terminate a signal generated by kinases activity. Due to counterbalancing the function of phosphorylation, the protein phosphatases are very important to signal transduction processes and thus the control of phosphatase activity is as significant as kinases, in the regulation of a plethora of cellular processes. In general, the protein phosphatases are comprised of a catalytic subunit with one or more regulatory and/or targeting subunits associated with it. The Protein Phosphatase 2A (PP2A), a member of serine/threonine phosphatases family, is ubiquitously expressed a remarkably conserved enzyme in the cell. Its catalytic activity has been highly regulated and may have enormous therapeutic potential which is still untapped. It has specificities for a number of substrates which witnessed its involvement in various signalling modules of cell cycle regulation, cell morphology and development. Thus it can be an appropriate target for studying different diseases associated with abnormal signal transduction pathways such as neurodegenerative diseases and malignancies. This review will focus on the structure and regulatory pathways of PP2A. The de-regulation of PP2A in some specific pathology such as Cancer, Heart diseases, Neurodegenerative disorders and Diabetes will also be touched upon.

摘要

有大量的信号通路负责在细胞内传递信息。尽管细胞信号被认为主要由蛋白激酶“级联效应”控制;但它们的拮抗剂蛋白磷酸酶在信号转导中也起着至关重要的双重作用。通过去磷酸化信号通路中涉及的蛋白质,磷酸酶可能导致其激活,有时它们也可能终止激酶活性产生的信号。由于磷酸化作用的平衡,蛋白磷酸酶对于信号转导过程非常重要,因此磷酸酶活性的控制与激酶一样重要,在调节众多细胞过程中起着重要作用。一般来说,蛋白磷酸酶由一个或多个调节和/或靶向亚基与一个催化亚基组成。蛋白磷酸酶 2A(PP2A)是丝氨酸/苏氨酸磷酸酶家族的成员,在细胞中广泛表达,是一种高度保守的酶。其催化活性受到高度调节,可能具有巨大的治疗潜力尚未被开发。它对许多底物具有特异性,见证了它参与细胞周期调控、细胞形态和发育等多种信号模块。因此,它可以成为研究与异常信号转导途径相关的不同疾病的合适靶点,如神经退行性疾病和恶性肿瘤。本综述将重点介绍 PP2A 的结构和调节途径。还将涉及 PP2A 在某些特定病理学中的失调,如癌症、心脏病、神经退行性疾病和糖尿病。

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