MyoD binds to Mos and inhibits the Mos/MAP kinase pathway.
When ectopically expressed, the serine/threonine kinase Mos can induce oncogenic transformation of somatic cells by direct phosphorylation of MAP kinase/ERK kinase (MEK1), activating the mitogen-activated protein kinases ERK1 and ERK2. On the other hand, overexpression of Mos in C2C12 myoblasts is not transforming. Mos activates myogenic differentiation by promoting heterodimerization of the MyoD/E12 proteins, increasing the expression of myogenic markers and the positive autoregulatory loop of MyoD. In this study, we show that in myogenic cells, the mitogenic and oncogenic signalling from the Mos/MEK/ERK pathway is suppressed by MyoD through the formation of a heterotrimeric complex.
Solhonne
B
B
Laboratoire de Génétique Oncologique UMR 1599 CNRS, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94800, Villejuif, France.
Lenormand
J L
JL
Pelpel
K
K
Leibovitch
M P
MP
Leibovitch
S A
SA
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D017232:Oncogene Proteins v-mos / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D014162:Transfection
D017570:MyoD Protein; D017232:Oncogene Proteins v-mos; D008156:Luciferases; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases