2 SERUM RESPONSE ELEMENTS MEDIATE TRANSCRIPTIONAL REPRESSION OF HUMANSMOOTH-MUSCLE ALPHA-ACTIN PROMOTER IN RAS-TRANSFORMED CELLS

The mechanism by which activated uas expression leads to repression ge nes specific actin filament proteins not understood, However, these ch anges associated with loss of organized actin filaments, are necessary to maintain the transformed phenotype. The human smooth muscle (sm) a lpha-actin promoter is repressed in ras-transformed fibroblast cells a nd derepressed in revertant cell lines. In this study, we demonstrate that two serum response elements (SREs) present in the alpha-actin pro moter are required for transcriptional repression in ras-transformed c ells and the two SREs act synergistically to repress heterologous prom oters 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 tran scription factors may play a role in repressing alpha-actin promoter i n uas-transformed cells.