These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: cAMP and tumor necrosis factor competitively regulate transcriptional activation through and nuclear factor binding to the cAMP-responsive element/activating transcription factor element of the endothelial leukocyte adhesion molecule-1 (E-selectin) promoter.
    Author: De Luca LG, Johnson DR, Whitley MZ, Collins T, Pober JS.
    Journal: J Biol Chem; 1994 Jul 29; 269(30):19193-6. PubMed ID: 7518452.
    Abstract:
    The cAMP-responsive element/activating transcription factor (CRE/ATF) element (also known as NF-ELAM1) of the endothelial leukocyte adhesion molecule-1 (ELAM-1) promoter is necessary for full cytokine responsiveness. It differs from a consensus cAMP-responsive element (CRE) by 1 nucleotide (G-->A conversion) and does not mediate transcriptional activation in response to cAMP. We reported previously that cAMP actually decreases ELAM-1 synthesis induced by tumor necrosis factor (TNF). We now show that cAMP decreases the ELAM-1 promoter response to TNF in transient transfection assays in bovine aortic endothelial cells and that cAMP-mediated inhibition maps to the CRE/ATF element. Electrophoretic mobility shift assays using the ELAM-1 CRE/ATF DNA sequence reveal three complexes. Antibody supershift assays suggest the slowest migrating form (complex 1) contains ATF2, the middle form (complex 2) contains ATF2 and c-Jun, and the fastest migrating form (complex 3) contains a CRE-binding protein. TNF increases c-Jun-containing complex 2 while diminishing complex 1, whereas cAMP decreases complex 2 and increases complex 1. Complex 3 is unchanged by either treatment, and the CRE-binding protein is not phosphorylated. Our data suggest that a change in the composition of the proteins binding to the CRE/ATF promoter element contributes to the competing effects of TNF and cAMP on ELAM-1 gene expression.
    [Abstract] [Full Text] [Related] [New Search]