Two serum response elements mediate transcriptional repression of human smooth muscle alpha-actin promoter in ras-transformed cells.
The mechanism by which activated ras oncogene expression leads to repression of genes encoding specific actin filament proteins is not understood. However, these changes associated with loss of organized actin filaments, are necessary to maintain the transformed phenotype. The human smooth muscle (sm) alpha-actin promoter is repressed in ras-transformed fibroblast cells and derepressed in revertant cell lines. In this study, we demonstrate that two serum response elements (SREs) present in the alpha-actin promoter are required for transcriptional repression in ras-transformed cells and the two SREs act synergistically to repress heterologous promoters in a ras-transformation dependent manner. Serum response factor (SRF), which can bind to the sm alpha-actin SREs, restores alpha-actin promoter activity in ras-transformed cells. c-Fos, c-Jun and YY1 also repress alpha-actin promoter through SREs, suggesting that these transcription factors may play a role in repressing alpha-actin promoter in ras-transformed cells.
Bushel
P
P
Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Kim
J H
JH
Chang
W
W
Catino
J J
JJ
Ruley
H E
HE
Kumar
C C
CC
D000199:Actins / Q000235:genetics*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000737:chemistry; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology; D017384:Sequence Deletion; D026362:Serum Response Factor; D014158:Transcription, Genetic
D000199:Actins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D026362:Serum Response Factor