Tafesh-Edwards Ghada, Eleftherianos Ioannis
Infection and Innate Immunity Lab, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, Science and Engineering Hall, 800 22nd Street NW, Washington DC, 20052, USA.
Infection and Innate Immunity Lab, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, Science and Engineering Hall, 800 22nd Street NW, Washington DC, 20052, USA.
Immunol Lett. 2020 Oct;226:7-11. doi: 10.1016/j.imlet.2020.06.017. Epub 2020 Jun 26.
As members of the mitogen-activated protein kinase (MAPK) family, the c-Jun N-terminal kinases (JNKs) regulate cell responses to a wide range of extrinsic and intrinsic insults, including irradiation, reactive oxygen species (ROS), DNA damage, heat, bacterial antigens, and inflammatory cytokines. Particularly, JNK signaling regulates and promotes many important physiological processes that influence metabolic and tissue homeostasis, cell death/survival, and cell damage repair and ultimately impacts the lifespan of an organism. This diverse functionality causes a variety of tissue-specific and context-specific cellular responses, mediated by various cross talks between JNK and other cellular signaling pathways. Thus, highlighting its significance as a determinant of stress responses, JNK loss-of-function mutations have been implicated in a multitude of pathologies, including neurodegenerative diseases, diabetes, and cancer. Because JNK functions are specified in a context-dependent manner and can greatly vary, the underlying causes for these different outcomes remain largely unresolved despite the gained knowledge of many regulatory roles of JNK signaling during the past two decades. In Drosophila melanogaster, JNK signaling is conserved and required for immune responses, as well as the development for morphogenetic processes (embryonic dorsal closure and thorax closure). Therefore, Drosophila innate immunity provides the ideal model to understand the complex mechanisms underlying JNK activation and regulation. In the following, we review studies in Drosophila that highlight several mechanisms by which JNK signaling influences immunity and homeostasis.
作为丝裂原活化蛋白激酶（MAPK）家族的成员，c-Jun氨基末端激酶（JNKs）可调节细胞对多种外在和内在刺激的反应，包括辐射、活性氧（ROS）、DNA损伤、热、细菌抗原和炎性细胞因子。特别是，JNK信号传导调节并促进许多重要的生理过程，这些过程影响代谢和组织稳态、细胞死亡/存活以及细胞损伤修复，并最终影响生物体的寿命。这种多样的功能会导致由JNK与其他细胞信号通路之间的各种相互作用介导的多种组织特异性和背景特异性细胞反应。因此，JNK功能丧失突变与多种病理学有关，包括神经退行性疾病、糖尿病和癌症，这突出了其作为应激反应决定因素的重要性。由于JNK的功能是以依赖于背景的方式指定的，并且可能有很大差异，尽管在过去二十年中对JNK信号传导的许多调节作用有了更多了解，但这些不同结果的根本原因在很大程度上仍未得到解决。在黑腹果蝇中，JNK信号传导对于免疫反应以及形态发生过程（胚胎背侧闭合和胸部闭合）的发育是保守且必需的。因此，果蝇先天免疫为理解JNK激活和调节的复杂机制提供了理想模型。在下文中，我们回顾了果蝇中的研究，这些研究突出了JNK信号传导影响免疫和稳态的几种机制。
