Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425-5050, USA.
Antioxid Redox Signal. 2012 Dec 15;17(12):1728-37. doi: 10.1089/ars.2012.4640. Epub 2012 Jun 13.
The family of glutathione S-transferases (GSTs) is part of a cellular Phase II detoxification program composed of multiple isozymes with functional human polymorphisms that have the capacity to influence individual response to drugs and environmental stresses. Catalytic activity is expressed through GST dimer-mediated thioether conjugate formation with resultant detoxification of a variety of small molecule electrophiles.
More recent work indicates that in addition to the classic catalytic functions, specific GST isozymes have other characteristics that impact cell survival pathways in ways unrelated to detoxification. These characteristics include the following: regulation of mitogen-activated protein kinases; facilitation of the addition of glutathione to cysteine residues in certain proteins (S-glutathionylation); as a novel cellular partner of the human papilloma virus-16 E7 oncoprotein playing a pivotal role in preventing cell death in infected human cells; mitogenic influence in myeloproliferative pathways; participant in the process of cocaine addiction.
Some of these functions have provided a platform for targeting GST with novel small molecule therapeutics, particularly in cancer where evidence of clinical applications is emerging.
Our evolving understanding of the GST superfamily and their divergent expression patterns in individuals make them attractive candidates for translational studies in a variety of human pathologies. In addition, their role in regulating cell fate in signaling and cell death pathways has opened up a significant functional complexity that extends well beyond standard detoxification reactions.
谷胱甘肽 S-转移酶 (GST) 家族是细胞 Phase II 解毒方案的一部分，由多种同工酶组成，这些同工酶具有功能性的人类多态性，能够影响个体对药物和环境应激的反应。催化活性通过 GST 二聚体介导的硫醚缀合物形成来表达，导致各种小分子亲电体的解毒。
最近的研究表明，除了经典的催化功能外，特定的 GST 同工酶还具有其他特征，这些特征通过与解毒无关的方式影响细胞存活途径。这些特征包括以下几个方面：调节有丝分裂原激活的蛋白激酶；促进特定蛋白质中半胱氨酸残基上的谷胱甘肽的添加（S-谷胱甘肽化）；作为人乳头瘤病毒 16 E7 癌蛋白的新型细胞伴侣，在感染的人类细胞中防止细胞死亡方面发挥关键作用；在骨髓增生性途径中的促有丝分裂作用；可卡因成瘾过程的参与者。
其中一些功能为 GST 提供了一个新的小分子治疗靶点的平台，特别是在癌症方面，已经有证据表明这种治疗方法具有临床应用前景。
我们对 GST 超家族的不断深入理解及其在个体中的不同表达模式，使它们成为各种人类病理的转化研究的有吸引力的候选者。此外，它们在调节信号和细胞死亡途径中的细胞命运方面的作用开辟了一个显著的功能复杂性，远远超出了标准的解毒反应。
