Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Int J Mol Sci. 2018 Nov 20;19(11):3657. doi: 10.3390/ijms19113657.
c-Jun-N-terminal kinase (JNK) activity plays a critical role in modulating cell death, which depends on the level and duration of JNK activation. The kinase cascade from MAPkinase kinase kinase (MAP3K) to MAPkinase kinase (MAP2K) to MAPKinase (MAPK) can be regulated by a number of direct and indirect post-transcriptional modifications, including acetylation, ubiquitination, phosphorylation, and their reversals. Recently, a JNK-mitochondrial SH3-domain binding protein 5 (SH3BP5/SAB)-ROS activation loop has been elucidated, which is required to sustain JNK activity. Importantly, the level of SAB expression in the outer membrane of mitochondria is a major determinant of the set-point for sustained JNK activation. SAB is a docking protein and substrate for JNK, leading to an intramitochondrial signal transduction pathway, which impairs electron transport and promotes reactive oxygen species (ROS) release to sustain the MAPK cascade.
c-Jun-N 末端激酶（JNK）活性在调节细胞死亡中起着关键作用，这取决于 JNK 激活的水平和持续时间。从 MAP 激酶激酶激酶（MAP3K）到 MAP 激酶激酶（MAP2K）到 MAP 激酶（MAPK）的激酶级联可以通过许多直接和间接的转录后修饰来调节，包括乙酰化、泛素化、磷酸化及其逆转。最近，已经阐明了 JNK-线粒体 SH3 结构域结合蛋白 5（SH3BP5/SAB）-ROS 激活环，该激活环是维持 JNK 活性所必需的。重要的是，线粒体外膜中 SAB 的表达水平是维持 JNK 激活的设定点的主要决定因素。SAB 是 JNK 的对接蛋白和底物，导致线粒体内部信号转导途径，该途径会损害电子传递并促进活性氧（ROS）释放，以维持 MAPK 级联。
