Two serum response elements mediate transcriptional repression of human smooth muscle α-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) α-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 α-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 α-actin SREs, restores α-actin promoter activity in ras-transformed cells. c-Fos, c-Jun and YY1 also repress α-actin promoter through SREs, suggesting that these transcription factors may play a role in repressing α-actin promoter in ras-transformed cells.