Weiss Carsten, Schneider Sandra, Wagner Erwin F, Zhang Xiaohong, Seto Edward, Bohmann Dirk
Department of Biomedical Genetics, University of Rochester, Rochester, NY 14642, USA.
EMBO J. 2003 Jul 15;22(14):3686-95. doi: 10.1093/emboj/cdg364.
The AP-1 transcription factor c-Jun is a prototypical nuclear effector of the JNK signal transduction pathway. The integrity of JNK phosphorylation sites at serines 63/73 and at threonines 91/93 in c-Jun is essential for signal-dependent target gene activation. We show that c-Jun phosphorylation mediates dissociation of an inhibitory complex, which is associated with histone deacetylase 3 (HDAC3). The subsequent events that ultimately cause increased mRNA synthesis are independent of c-Jun phosphorylation and its interaction with JNK. These findings provide an 'activation by de-repression' model as an explanation for the stimulatory function of JNK on c-Jun.
AP-1转录因子c-Jun是JNK信号转导通路的典型核效应因子。c-Jun中丝氨酸63/73和苏氨酸91/93处JNK磷酸化位点的完整性对于信号依赖性靶基因激活至关重要。我们发现c-Jun磷酸化介导了一种抑制复合物的解离,该复合物与组蛋白去乙酰化酶3(HDAC3)相关。最终导致mRNA合成增加的后续事件独立于c-Jun磷酸化及其与JNK的相互作用。这些发现提供了一种“去抑制激活”模型,以解释JNK对c-Jun的刺激功能。