Transformation by activated ras or fos prevents myogenesis by inhibiting expression of MyoD1.
Transformation of myoblasts by activated ras inhibits myogenic differentiation. We demonstrate that this oncogene inhibits expression of the muscle regulatory factors MyoD1 and myogenin. Expression of retroviral-encoded MyoD1 in ras-transformed myoblasts leads to the re-expression of both terminal differentiation markers and lineage markers expressed in proliferating myoblasts (including endogenous MyoD1 and myogenin), suggesting that ras inhibits myogenic differentiation in a manner dependent on the loss of MyoD1 expression. In addition, we show that fos transformation of myoblasts inhibits muscle differentiation by a similar mechanism.
Lassar
A B
AB
Department of Genetics, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Thayer
M J
MJ
Overell
R W
RW
Weintraub
H
H
D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D011905:Genes, ras; D066298:In Vitro Techniques; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000502:physiology*; D017570:MyoD Protein; D018008:Myogenin; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos; D014170:Transformation, Genetic
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos