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PMID: 2847147 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 85 ·No. 21 ·1988-11-00 ·Pages 7922-6

Deutsch PJ, Hoeffler JP, Jameson JL, Habener JF

Abstract

cAMP and phorbol esters mediate cellular metabolism by the activation of distinct signal transduction pathways consisting of a cascade of sequential protein phosphorylations. An important consequence of the activation of these pathways is the stimulation of gene transcription by way of interactions of specific proteins with DNA control elements. The 8-base-pair (bp) DNA consensus sequence TGACGTCA [cAMP response element (cAMP-RE)] has been shown to confer cAMP responsivity on transcription from various promoters, and the closely related 7-bp consensus sequence TGA-(C or G)TCA [phorbol 12-myristate 13-acetate response element (PMA-RE)] lends transcriptional responsiveness to phorbol esters. In the JEG-3 placental cell line we find that several variants of the cAMP-REs fused to a gonadotropin alpha promoter chloramphenicol acetyltransferase reporter gene mediate responsiveness to cAMP but not to phorbol esters. The PMA-RE is responsive to phorbol esters but also imparts submaximal sensitivity to cAMP in the JEG-3 cells and in the Hep G2 hepatoma cell line. The transcriptional activities of cAMP-RE and PMA-RE are markedly influenced by the composition of the neighboring bases, but different sequences are permissive for the activity of the cAMP-RE versus the PMA-RE. The two signaling agents together display a supraadditive effect on reporter genes containing active PMA-REs but not cAMP-REs. Gel-mobility-shift and UV cross-linking analyses show that distinct proteins bind to the two control elements. One protein of 38 kDa binds to the cAMP-RE and several proteins of 48-84 kDa bind to the PMA-RE.

MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate/pharmacology Animals Base Sequence Cell Line Cells, Cultured Cyclic AMP/pharmacology DNA/metabolism DNA-Binding Proteins/metabolism Phorbol Esters/pharmacology Plasmids Transcription, Genetic Transfection
Chemicals
DNA-Binding Proteins Phorbol Esters 8-Bromo Cyclic Adenosine Monophosphate DNA Cyclic AMP
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Deutsch P J
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston.
Hoeffler J P
Jameson J L
Habener J F
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.85.21.7922
Published
1988-11-00
Pages
7922-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC282325
Subset
IM
Grants
NIDDK NIH HHS · DK-25532 · United States
External Links
PubMed source DOI: 10.1073/pnas.85.21.7922 PMC Full Text View journal details
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