Perry R L, Parker M H, Rudnicki M A
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Mol Cell. 2001 Aug;8(2):291-301. doi: 10.1016/s1097-2765(01)00302-1.
To elucidate the mechanism through which MAPK signaling regulates the MyoD family of transcription factors, we investigated the role of the signaling intermediate MEK1 in myogenesis. Transfection of activated MEK1 strongly repressed gene activation and myogenic conversion by the MyoD family. This repression was not mediated by direct phosphorylation of MyoD or by changes in MyoD stability or subcellular distribution. Deletion mapping revealed that MEK1-mediated repression required the MyoD amino-terminal transactivation domain. Moreover, activated MEK1 was nuclearly localized and bound a complex containing MyoD in a manner that is dependent on the presence of the MyoD amino terminus. Together, these data demonstrate that MEK1 signaling has a strong negative effect on MyoD activity via a novel mechanism involving binding of MEK1 to the nuclear MyoD transcriptional complex.
为阐明丝裂原活化蛋白激酶（MAPK）信号传导调节转录因子MyoD家族的机制，我们研究了信号中间体MEK1在肌生成中的作用。转染活化的MEK1可强烈抑制MyoD家族的基因激活和肌源性转化。这种抑制作用不是通过MyoD的直接磷酸化、MyoD稳定性的改变或亚细胞分布的变化介导的。缺失图谱分析表明，MEK1介导的抑制作用需要MyoD氨基末端反式激活结构域。此外，活化的MEK1定位于细胞核，并以依赖于MyoD氨基末端存在的方式与包含MyoD的复合物结合。这些数据共同表明，MEK1信号传导通过一种涉及MEK1与细胞核MyoD转录复合物结合的新机制，对MyoD活性产生强烈的负面影响。
