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Title: Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Author: Chiu R, Imagawa M, Imbra RJ, Bockoven JR, Karin M. Journal: Nature; ; 329(6140):648-51. PubMed ID: 2821407. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]