Activated MEK1 binds the nuclear MyoD transcriptional complex to repress transactivation

被引:103
作者
Perry, RLS
Parker, MH
Rudnicki, MA [1 ]
机构
[1] McMaster Univ, Dept Biol, Hamilton, ON, Canada
[2] McMaster Univ, Med Sci Grad Program, Hamilton, ON, Canada
[3] Ottawa Hlth Res Inst, Program Mol Med, Ottawa, ON, Canada
基金
加拿大健康研究院; 美国国家卫生研究院;
关键词
D O I
10.1016/S1097-2765(01)00302-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:291 / 301
页数:11
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