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A cyclic AMP- and phorbol ester-inducible DNA element

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Abstract

Many cellular processes are regulated by hormones and neuro-transmitters which interact with cell-surface receptors to produce intracellular second messengers that activate protein kinases. Cyclic (c) AMP is a second messenger whose intracellular level is determined by receptor-mediated activation or inhibition of adeny-late cyclase1,2. Phorbol esters directly activate protein kinase C, a Ca2+ and phospholipid-dependent protein kinase3 and a component of a different second messenger system, the phosphatidylinositol pathway4. Proenkephalin messenger RNA levels are regulated in response to cAMP analogues5, activators of adenylate cyclase6, nicotinic agonists7 and depolarization8, suggesting that expression of the gene encoding proenkephalin is regulated by trans-synaptic events involving cell-surface-receptor activation. Here we report that cAMP analogues and activators of adenylate cyclase regulate a proenkephalin-chloramphenicol acetyl trans-ferase fusion gene when transiently expressed in tissue culture cells. Phorbol ester regulates the fusion gene in a similar fashion, but requires the presence of phosphodiesterase inhibitors for large effects. The DNA sequences required for regulation by both cAMP and phorbol ester map to the same 37-base pair (bp) region located 107–71 bp 5′ to the mRNA cap site of the proenkephalin gene. This highly conserved region is composed of three closely related 12-bp sequences and has properties similar to those of previously characterized transcriptional enhancers.

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Author notes

  1. Audrey Seasholtz and Edward Herbert: Institute for Advanced Biomedical Research, The Oregon Health Sciences University, 3181 S.W. Jackson Park Road, Portland, Oregon 97201, USA

Authors and Affiliations

  1. Departments of Molecular Biology and Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

    Michael Comb, Neal C. Birnberg, Audrey Seasholtz, Edward Herbert & Howard M. Goodman

Authors
  1. Michael Comb
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  2. Neal C. Birnberg
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  3. Audrey Seasholtz
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  4. Edward Herbert
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  5. Howard M. Goodman
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Comb, M., Birnberg, N., Seasholtz, A. et al. A cyclic AMP- and phorbol ester-inducible DNA element. Nature 323, 353–356 (1986). https://doi.org/10.1038/323353a0

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  • DOI: https://doi.org/10.1038/323353a0

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