Activated MEK1 binds the nuclear MyoD transcriptional complex to repress transactivation
Activated MEK1 binds the nuclear MyoD transcriptional complex to repress transactivation
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DOI：
10.1016/s1097-2765(01)00302-1
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发表时间：
2001-08-01
期刊：
影响因子：
16
通讯作者：
Rudnicki, MA
中科院分区：
文献类型：
--
作者：
Perry, RLS;Parker, MH;Rudnicki, MA
为了阐明MAPK信号调节MyoD家族转录因子的机制，我们研究了信号中间体MEK 1在肌发生中的作用。转染活化的MEK 1强烈抑制基因激活和MyoD家族的肌原性转化。这种抑制不是由MyoD的直接磷酸化或MyoD稳定性或亚细胞分布的变化介导的。缺失图谱显示，MEK1介导的阻遏需要MyoD氨基末端反式激活结构域。此外，活化的MEK1被核定位并以依赖于MyoD氨基末端的存在的方式结合含有MyoD的复合物。总之，这些数据表明，MEK1信号转导通过一种涉及MEK1与核MyoD转录复合物结合的新机制对MyoD活性具有强烈的负面影响。
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.