A Harvey-ras responsive transcription element is also responsive to a tumour-promoter and to serum.
The ras oncogenes are implicated in the onset of some human tumours, and in cellular proliferation and terminal differentiation. The ras proteins are plasma membrane bound transducers of signals between the outside of the cell and unknown targets in the cell. Identifying these targets and understanding how they are regulated will have a major impact on our understanding of the molecular basis of transformation. We have already shown that c-Ha-ras and the tumor promoter TPA (12-o-tetradecanoyl phorbol-13-acetate) can activate a transcriptional enhancer. We now report the identification of a short sequence in the polyoma virus (Py) enhancer which mediates Ha-ras activation, and show that this sequence (ras responsive element, RRE) also mediates activation by TPA and serum. This responsive element is a specific binding-site for the mouse transcription factor PEA1 (ref. 4 and below) and for the jun oncogene (ref. 5 and M. Karin, personal communication). These results are in keeping with a role for ras protein in signal transduction from outside the cell to a transcription factor in the nucleus, through protein kinase C. The striking similarity between RRE and DNA sequences present in the promoter regions of a number of transformation-related genes suggests that deregulated activation of RRE is a critical event in transformation.
Imler
J L
JL
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique, INSERM, Faculté de Médecine, Strasbourg, France.
Schatz
C
C
Wasylyk
C
C
Chatton
B
B
Wasylyk
B
B
D001769:Blood; D004274:DNA, Recombinant; D004279:DNA, Viral / Q000235:genetics; D004742:Enhancer Elements, Genetic; D009154:Mutation; D011120:Polyomavirus / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011519:Proto-Oncogenes; D013539:Simian virus 40 / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D004274:DNA, Recombinant; D004279:DNA, Viral; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate