Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters.
Protein kinase C is important in the transduction of signals generated at the plasma membrane. The physiological activators of protein kinase C are diacylglycerols, and the tumour-promoting phorbol esters, such as 12-O-tetradecanoyl-phorbol-14 acetate (TPA), constitute another group of specific activators. Many cellular substrates for phosphorylation by protein kinase C have been described, but proteins that directly control transcription in response to protein kinase C activation are yet to be identified. TPA treatment leads to induction of various proto-oncogenes, growth factor genes, and genes encoding secreted proteases. In addition. TPA increases the activity of viral enhancer elements. To identify trans-acting factors that mediate the transcriptional response to TPA we chose the simian virus 40 (SV40) enhancer as a model, because it is known to be composed of several discrete cis-acting elements which are recognized by multiple transacting factors. We report here that the SV40 enhancer contains at least four different TPA responsive elements whose activity is dependent on cell-type. The induction response is likely to involve at least two distinct post-translational steps which modulate the activity of the proteins that recognize these elements.
Chiu
R
R
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.
Imagawa
M
M
Imbra
R J
RJ
Bockoven
J R
JR
Karin
M
M
D001483:Base Sequence; D002460:Cell Line; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009154:Mutation; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011519:Proto-Oncogenes; D013539:Simian virus 40 / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D010703:Phorbol Esters; D011493:Protein Kinase C; D003850:Deoxyribonuclease I; D013755:Tetradecanoylphorbol Acetate