Lamb Jennifer A, Ventura Juan-Jose, Hess Patricia, Flavell Richard A, Davis Roger J
Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry & Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Mol Cell. 2003 Jun;11(6):1479-89. doi: 10.1016/s1097-2765(03)00203-x.
The c-Jun NH(2)-terminal kinase (JNK) can cause cell death by activating the mitochondrial apoptosis pathway. However, JNK is also capable of signaling cell survival. The mechanism that accounts for the dual role of JNK in apoptosis and survival signaling has not been established. Here we demonstrate that JNK-stimulated survival signaling can be mediated by JunD. The JNK/JunD pathway can collaborate with NF-kappaB to increase antiapoptotic gene expression. This observation accounts for the ability of JNK to cause either survival or apoptosis in different cellular contexts. Furthermore, these data illustrate the general principal that signal transduction pathway integration is critical for the ability of cells to mount an appropriate biological response to a specific challenge.
c-Jun氨基末端激酶(JNK)可通过激活线粒体凋亡途径导致细胞死亡。然而,JNK也能够发出细胞存活信号。JNK在凋亡和存活信号传导中发挥双重作用的机制尚未明确。在此,我们证明JNK刺激的存活信号可由JunD介导。JNK/JunD途径可与核因子κB协作以增加抗凋亡基因的表达。这一观察结果解释了JNK在不同细胞环境中导致存活或凋亡的能力。此外,这些数据说明了一个普遍原则,即信号转导途径整合对于细胞对特定刺激做出适当生物学反应的能力至关重要。