Veal Elizabeth A, Kritsiligkou Paraskevi
Newcastle University Biosciences Institute, Newcastle upon Tyne, NE2 4HH, UK.
Division of Redox Regulation, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany; Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
Curr Opin Chem Biol. 2024 Aug;81:102496. doi: 10.1016/j.cbpa.2024.102496. Epub 2024 Jul 2.
HO signals trigger adaptive responses affecting cell division, differentiation, migration, and survival. These signals are transduced by selective oxidation of cysteines on specific target proteins, with redox-sensitive cysteines now identified in many proteins, including both kinases and phosphatases. Assessing the contribution of these oxidation events to cell signalling presents several challenges including understanding how and when the selective oxidation of specific proteins takes place in vivo. In recent years, a combination of biochemical, structural, genetic, and computational approaches in fungi, plants, and animals have revealed different ways in which thiol peroxidases (peroxiredoxins) are bypassed or utilised in relaying these signals. Together, these mechanisms provide a conceptual framework for selectively oxidising proteins that will further advance understanding of how redox modifications contribute to health and disease.
HO信号触发影响细胞分裂、分化、迁移和存活的适应性反应。这些信号通过特定靶蛋白上半胱氨酸的选择性氧化进行转导,目前已在许多蛋白质(包括激酶和磷酸酶)中鉴定出对氧化还原敏感的半胱氨酸。评估这些氧化事件对细胞信号传导的贡献面临若干挑战,包括了解特定蛋白质的选择性氧化在体内如何以及何时发生。近年来,真菌、植物和动物中生物化学、结构、遗传和计算方法的结合揭示了硫醇过氧化物酶(过氧化物还原酶)在传递这些信号时被绕过或利用的不同方式。这些机制共同提供了一个选择性氧化蛋白质的概念框架,这将进一步推动我们对氧化还原修饰如何影响健康和疾病的理解。