Ding Tao, Zhou Ya, Long Runying, Chen Chao, Zhao Juanjuan, Cui Panpan, Guo Mengmeng, Liang Guiyou, Xu Lin
Special Key Laboratory of Gene Detection and Therapy of Guizhou Province, Zunyi, 563000 Guizhou China.
2Department of Immunology, Zunyi Medical University, Zunyi, 563000 Guizhou China.
Cell Biosci. 2019 Aug 27;9:70. doi: 10.1186/s13578-019-0329-4. eCollection 2019.
Dual-specificity phosphatases (DUSPs) are a subset of protein tyrosine phosphatases (PTPs), many of which dephosphorylate the residues of phosphor-serine/threonine and phosphor-tyrosine on mitogen-activated protein kinases (MAPKs), and hence are also referred to as MAPK phosphatases (MKPs). Homologue of Vaccinia virus H1 phosphatase gene clone 5 (HVH-5), also known as DUSP8, is a unique member of the DUSPs family of phosphatases. Accumulating evidence has shown that DUSP8 plays an important role in phosphorylation-mediated signal transduction of MAPK signaling ranging from cell oxidative stress response, cell apoptosis and various human diseases. It is generally believed that DUSP8 exhibits significant dephosphorylation activity against JNK, however, with the deepening of research, plenty of new literature reports that DUSP8 also has effective dephosphorylation activity on p38 MAPK and ERKs, successfully affects the transduction of MAPKs pathway, indicating that DUSP8 presents a unknown diversity of DUSPs family on distinct corresponding dephosphorylated substrates in different biological events. Therefore, the in-depth study of DUSP8 not only throws a new light on the multi-biological function of DUSPs, but also is much valuable for the reveal of complex pathobiology of clinical diseases. In this review, we provide a detail overview of DUSP8 phosphatase structure, biological function and expression regulation, as well as its role in related clinical human diseases, which might be help for the understanding of biological function of DUSP8 and the development of prevention, diagnosis and therapeutics in related human diseases.
双特异性磷酸酶（DUSPs）是蛋白酪氨酸磷酸酶（PTPs）的一个子集，其中许多可使丝裂原活化蛋白激酶（MAPKs）上的磷酸化丝氨酸/苏氨酸和磷酸化酪氨酸残基去磷酸化，因此也被称为MAPK磷酸酶（MKPs）。痘苗病毒H1磷酸酶基因克隆5（HVH-5）的同源物，也称为DUSP8，是磷酸酶DUSPs家族的一个独特成员。越来越多的证据表明，DUSP8在MAPK信号的磷酸化介导信号转导中发挥重要作用，涉及细胞氧化应激反应、细胞凋亡和各种人类疾病。一般认为DUSP8对JNK具有显著的去磷酸化活性，然而，随着研究的深入，大量新文献报道DUSP8对p38 MAPK和ERK也具有有效的去磷酸化活性，成功影响MAPKs通路的转导，表明DUSP8在不同生物事件中对不同相应去磷酸化底物呈现出DUSPs家族未知的多样性。因此，对DUSP8的深入研究不仅为DUSPs的多种生物学功能提供了新的线索，也对揭示临床疾病复杂的病理生物学具有重要价值。在这篇综述中，我们详细概述了DUSP8磷酸酶的结构、生物学功能、表达调控及其在相关人类临床疾病中的作用，这可能有助于理解DUSP8的生物学功能以及相关人类疾病的预防、诊断和治疗的发展。
