Suppression of Ras transformation by serum response factor.
Serum response factor (SRF) is a nuclear transcription factor that binds to the serum response element (SRE) found in the promoter regions of a number of growth factor-inducible genes, as well as muscle-specific genes. The smooth muscle alpha-actin promoter contains two SRE sequences that can bind to SRF. Its expression is repressed in Ras-transformed fibroblast cells and derepressed in revertant cells. In this study, we demonstrate that SRF can activate alpha-actin expression in Ras-transformed cells and that overexpression of SRF in Ras-transformed cells can revert their transformed phenotype. The ability of SRF to bind to the SRE was required for this effect, since mutations that inhibit DNA binding abolish SRF's ability to activate alpha-actin expression and suppress transformation by the ras oncogene. These results show that SRF, thought to be involved in stimulation of cell growth through activation of growth factor-inducible genes, can actually have the opposite effect and suggest a novel mechanism for suppression of transformation by Ras.
Kim
J H
JH
Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
Johansen
F E
FE
Robertson
N
N
Catino
J J
JJ
Prywes
R
R
Kumar
C C
CC
D000199:Actins / Q000235:genetics; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D011905:Genes, ras; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D026362:Serum Response Factor; D014157:Transcription Factors / Q000502:physiology*
D000199:Actins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014157:Transcription Factors