Cyclic AMP- and phorbol ester-induced transcriptional activation are mediated by the same enhancer element in the human vasoactive intestinal peptide gene

J. Stephen Fink, Menno Verhave, Kevin Walton, Gail Mandel, Richard Goodman

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Transcription of the human vasoactive intestinal peptide (VIP) gene is regulated by both cyclic AMP and phorbol esters. A 17-nucleotide enhancer element within the human VIP gene mediates transcriptional activation by both phorbol esters and forskolin. Mutations of this element decrease responses to both agents, suggesting that the trans-acting proteins that mediate both modes of transcriptional regulation have similar DNA-binding characteristics. The response of the VIP enhancer element to forskolin, but not to 12-O-tetradecanoylphorbol-13-acetate, was attenuated by treatment with a recombinant inhibitor of the cAMP-dependent protein kinase, suggesting that the cAMP-dependent protein kinase and protein kinase C second messenger pathways that converge on this single enhancer element are distinct. The transcriptional activator cAMP-responsive element-binding (CREB) proteins and the c-fos·c-Jun complex interact with the VIP enhancer. The dual second messenger responses of the VIP gene may result from the interaction of this second messenger enhancer with different transcriptional activator proteins.

Original languageEnglish (US)
Pages (from-to)3882-3887
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number6
StatePublished - Feb 25 1991

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Vasoactive Intestinal Peptide
Phorbol Esters
Cyclic AMP
Transcriptional Activation
Genes
Chemical activation
Second Messenger Systems
Colforsin
Cyclic AMP-Dependent Protein Kinases
Response Elements
Tetradecanoylphorbol Acetate
Transcription
Chemical elements
Protein Kinase C
Carrier Proteins
Proteins
Acetates
Nucleotides
Mutation
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cyclic AMP- and phorbol ester-induced transcriptional activation are mediated by the same enhancer element in the human vasoactive intestinal peptide gene. / Fink, J. Stephen; Verhave, Menno; Walton, Kevin; Mandel, Gail; Goodman, Richard.

In: Journal of Biological Chemistry, Vol. 266, No. 6, 25.02.1991, p. 3882-3887.

Research output: Contribution to journalArticle

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AB - Transcription of the human vasoactive intestinal peptide (VIP) gene is regulated by both cyclic AMP and phorbol esters. A 17-nucleotide enhancer element within the human VIP gene mediates transcriptional activation by both phorbol esters and forskolin. Mutations of this element decrease responses to both agents, suggesting that the trans-acting proteins that mediate both modes of transcriptional regulation have similar DNA-binding characteristics. The response of the VIP enhancer element to forskolin, but not to 12-O-tetradecanoylphorbol-13-acetate, was attenuated by treatment with a recombinant inhibitor of the cAMP-dependent protein kinase, suggesting that the cAMP-dependent protein kinase and protein kinase C second messenger pathways that converge on this single enhancer element are distinct. The transcriptional activator cAMP-responsive element-binding (CREB) proteins and the c-fos·c-Jun complex interact with the VIP enhancer. The dual second messenger responses of the VIP gene may result from the interaction of this second messenger enhancer with different transcriptional activator proteins.

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