PDF(Pubmed)
Abstract：
JNK is named after c-Jun N-terminal kinase, as it is responsible for phosphorylating c-Jun. As a member of the mitogen-activated protein kinase (MAPK) family, JNK is also known as stress-activated kinase (SAPK) because it can be activated by extracellular stresses including growth factor, UV irradiation, and virus infection. Functionally, JNK regulates various cell behaviors such as cell differentiation, proliferation, survival, and metabolic reprogramming. Dysregulated JNK signaling contributes to several types of human diseases. Although the role of the JNK pathway in a single disease has been summarized in several previous publications, a comprehensive review of its role in multiple kinds of human diseases is missing. In this review, we begin by introducing the landmark discoveries, structures, tissue expression, and activation mechanisms of the JNK pathway. Next, we come to the focus of this work: a comprehensive summary of the role of the deregulated JNK pathway in multiple kinds of diseases. Beyond that, we also discuss the current strategies for targeting the JNK pathway for therapeutic intervention and summarize the application of JNK inhibitors as well as several challenges now faced. We expect that this review can provide a more comprehensive insight into the critical role of the JNK pathway in the pathogenesis of human diseases and hope that it also provides important clues for ameliorating disease conditions.
摘要：
JNK以c-JunN末端激酶命名，因为它负责磷酸化c-Jun。作为丝裂原活化蛋白激酶（MAPK）家族的成员，JNK也被称为应激激活激酶（SAPK），因为它可以被包括生长因子在内的细胞外应激激活。紫外线照射，和病毒感染。功能上,JNK调节各种细胞行为，如细胞分化，扩散,生存,和代谢重编程。JNK信号传导失调导致几种类型的人类疾病。虽然JNK通路在单一疾病中的作用已在几个以前的出版物中进行了总结，缺乏对其在多种人类疾病中的作用的全面审查。在这次审查中,我们首先介绍具有里程碑意义的发现，结构,组织表达，和JNK途径的激活机制。接下来,我们来到这项工作的重点：全面总结了JNK通路失调在多种疾病中的作用。除此之外，我们还讨论了目前靶向JNK途径进行治疗干预的策略，并总结了JNK抑制剂的应用以及目前面临的几个挑战。我们希望这篇综述可以更全面地了解JNK通路在人类疾病发病机制中的关键作用，并希望它也为改善疾病状况提供重要线索。
