Zhang Jie, Grek Christina, Ye Zhi-Wei, Manevich Yefim, Tew Kenneth D, Townsend Danyelle M
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina, USA.
Professor and Chairman, Department of Cell and Molecular Pharmacology, John C. West Chair of Cancer Research, Medical University of South Carolina, Charleston, South Carolina, USA.
Adv Cancer Res. 2014;122:143-75. doi: 10.1016/B978-0-12-420117-0.00004-9.
Glutathione S-transferase P (GSTP) is one member of the GST superfamily that is prevalently expressed in mammals. Known to possess catalytic activity through deprotonating glutathione allowing formation of thioether bonds with electrophilic substrates, more recent discoveries have broadened our understanding of the biological roles of this protein. In addition to catalytic detoxification, other properties so far ascribed to GSTP include chaperone functions, regulation of nitric oxide pathways, regulation of a variety of kinase signaling pathways, and participation in the forward reaction of protein S-glutathionylation. The expression of GSTP has been linked with cancer and other human pathologies and more recently even with drug addiction. With respect to human health, polymorphic variants of GSTP may determine individual susceptibility to oxidative stress and/or be critical in the design and development of drugs that have used redox pathways as a discovery platform.
谷胱甘肽S-转移酶P(GSTP)是谷胱甘肽S-转移酶超家族的成员之一,在哺乳动物中普遍表达。已知它通过使谷胱甘肽去质子化而具有催化活性,从而允许与亲电子底物形成硫醚键,最近的发现拓宽了我们对该蛋白质生物学作用的理解。除了催化解毒作用外,迄今为止归因于GSTP的其他特性还包括伴侣功能、一氧化氮途径的调节、多种激酶信号通路的调节以及参与蛋白质S-谷胱甘肽化的正向反应。GSTP的表达与癌症和其他人类疾病有关,最近甚至与药物成瘾有关。就人类健康而言,GSTP的多态性变体可能决定个体对氧化应激的易感性,和/或在以氧化还原途径为发现平台的药物设计和开发中起关键作用。