Activated MEK1 binds the nuclear MyoD transcriptional complex to repress transactivation.
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.
Perry
R L
RL
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Parker
M H
MH
Rudnicki
M A
MA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002458:Cell Fractionation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D017930:Genes, Reporter / Q000235:genetics; D015151:Immunoblotting; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection
D017570:MyoD Protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases