Oxidation processes in mitochondria and different environmental insults contribute to unwarranted accumulation of reactive oxygen species (ROS). These, in turn, rapidly damage intracellular lipids, proteins, and DNA, ultimately causing aging and several human diseases. Cells have developed different and very effective systems to control ROS levels. Among these, removal of excessive amounts is guaranteed by upregulated expression of various antioxidant enzymes, through activation of the NF-E2-Related Factor 2 (NRF2) protein. Here, we show that Mitogen Activated Protein Kinase 15 (MAPK15) controls the transactivating potential of NRF2 and, in turn, the expression of its downstream target genes. Specifically, upon oxidative stress, MAPK15 is necessary to increase NRF2 expression and nuclear translocation, by inducing its activating phosphorylation, ultimately supporting transactivation of cytoprotective antioxidant genes.

中文翻译：

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MAPK15 通过调节 NRF2 活性及其下游靶基因的表达来控制细胞对氧化应激的反应


线粒体的氧化过程和不同的环境损伤会导致活性氧（ROS）的不必要的积累。这些反过来又会迅速损害细胞内脂质、蛋白质和 DNA，最终导致衰老和多种人类疾病。细胞已经开发出不同且非常有效的系统来控制 ROS 水平。其中，通过激活 NF-E2 相关因子 2 (NRF2) 蛋白，上调各种抗氧化酶的表达，可以保证去除过量的物质。在这里，我们发现丝裂原激活蛋白激酶 15 (MAPK15) 控制 NRF2 的反式激活潜力，进而控制其下游靶基因的表达。具体来说，在氧化应激时，MAPK15 通过诱导其激活磷酸化来增加 NRF2 表达和核转位，最终支持细胞保护性抗氧化基因的反式激活。