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Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters

Nature volume 329, pages 648–651 (1987)Cite this article

Abstract

Protein kinase C is important in the transduction of signals generated at the plasma membrane. The physiological activators of protein kinase C are diacylglycerols1, and the tumour-promoting phorbol esters, such as 12-O-tetradecanoyI-phorbol-14 acetate (TPA), constitute another group of specific activators1,2. Many cellular substrates for phosphorylation by protein kinase C have been described1,3, 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-oncogenes4–7, growth factor genes7,8, and genes encoding secreted proteases9. In addition. TPA increases the activity of viral enhancer elements10–13. To identify trans-acting factors that mediate the transcriptional response to TPA we chose the simian virus 40 (SV40) enhancer14 as a model, because it is known to be composed of several discrete cis-acting elements15–18 which are recognized by multiple trans-acting factors19–21. 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.

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Author notes

  1. Richard J. Imbra

    Present address: Department of Environmental Medicine, New York University Medical Center, New York, New York, 10016, USA

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine and Center for Molecular Genetics, University of California, San Diego, La Jolla, California, 92093, USA

    Robert Chiu, Masayoshi Imagawa, Richard J. Imbra, John R. Bockoven & Michael Karin

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  1. Robert Chiu
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  2. Masayoshi Imagawa
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  3. Richard J. Imbra
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  4. John R. Bockoven
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  5. Michael Karin
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Chiu, R., Imagawa, M., Imbra, R. et al. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Nature 329, 648–651 (1987). https://doi.org/10.1038/329648a0

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