The c‐Jun‐N‐terminal‐kinase (JNK) family is highly conserved across species such as Drosophila, C. elegans, zebrafish and mammals, and plays a central role in hepatic physiologic and pathophysiologic responses. These responses range from cell death to cell proliferation and carcinogenesis, as well as metabolism and survival, depending on the specific context and duration of activation of the JNK signaling pathway. Recently, several investigators identified the key molecules in the JNK activation loop which include apoptosis signal‐regulating kinase (ASK1) and SH3‐domain binding protein 5 (Sab) and their involvement in acute or chronic liver disease models. Thus, regulating JNK activation through modulating the JNK activation loop may represent an important new strategy in the prevention and treatment of acute and chronic liver diseases. In this review, we will discuss the molecular pathophysiology of the JNK activation loop and its role in the pathogenesis of liver diseases. (Hepatology 2018;67:2013‐2024).

中文翻译：

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c-Jun-N-末端激酶信号在肝病病理生物学中的作用和机制的新见解

c-Jun-N-末端激酶 (JNK) 家族在果蝇、秀丽隐杆线虫、斑马鱼和哺乳动物等物种中高度保守，并在肝脏生理和病理生理反应中发挥核心作用。这些反应范围从细胞死亡到细胞增殖和致癌作用，以及代谢和存活，具体取决于 JNK 信号通路激活的特定背景和持续时间。最近，几位研究人员确定了 JNK 激活环中的关键分子，包括细胞凋亡信号调节激酶 (ASK1) 和 SH3 结构域结合蛋白 5 (Sab) 及其参与急性或慢性肝病模型。因此，通过调节 JNK 激活环来调节 JNK 激活可能代表了预防和治疗急慢性肝病的重要新策略。在这篇综述中，我们将讨论 JNK 激活环的分子病理生理学及其在肝病发病机制中的作用。（肝病学 2018；67：2013-2024）。