Lee In-Gyun, Lee Bong-Jin
Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
Antioxidants (Basel). 2023 Feb 20;12(2):531. doi: 10.3390/antiox12020531.
Aurora kinase A (AURKA), which is a member of serine/threonine kinase family, plays a critical role in regulating mitosis. AURKA has drawn much attention as its dysregulation is critically associated with various cancers, leading to the development of AURKA inhibitors, a new class of anticancer drugs. As the spatiotemporal activity of AURKA critically depends on diverse intra- and inter-molecular factors, including its interaction with various protein cofactors and post-translational modifications, each of these pathways should be exploited for the development of a novel class of AURKA inhibitors other than ATP-competitive inhibitors. Several lines of evidence have recently shown that redox-active molecules can modify the cysteine residues located on the kinase domain of AURKA, thereby regulating its activity. In this review, we present the current understanding of how oxidative modifications of cysteine residues of AURKA, induced by redox-active molecules, structurally and functionally regulate AURKA and discuss their implications in the discovery of novel AURKA inhibitors.
极光激酶A（AURKA）是丝氨酸/苏氨酸激酶家族的成员，在调节有丝分裂中起关键作用。AURKA因其失调与多种癌症密切相关而备受关注，这促使了一类新型抗癌药物——AURKA抑制剂的研发。由于AURKA的时空活性严重依赖于多种分子内和分子间因素，包括其与各种蛋白质辅助因子的相互作用以及翻译后修饰，因此除了ATP竞争性抑制剂外，还应利用这些途径中的每一条来开发新型AURKA抑制剂。最近有几条证据表明，具有氧化还原活性的分子可以修饰位于AURKA激酶结构域上的半胱氨酸残基，从而调节其活性。在这篇综述中，我们阐述了目前对由具有氧化还原活性的分子诱导的AURKA半胱氨酸残基的氧化修饰如何在结构和功能上调节AURKA的理解，并讨论了它们在新型AURKA抑制剂发现中的意义。
