An NFxB-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription (original) (raw)

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Rob Hooft van Huijsduijnen

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1

Glaxo Inc.

North Carolina, USA

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Glaxo Inc.

North Carolina, USA

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Received:

21 February 1991

Revision received:

29 April 1991

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James Whelan, Paola Ghersa, Rob Hooft van Huijsduijnen, John Gray, Gyan Chandra, Francois Talabot, John F. DeLamarter, An NF_x_B-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription, Nucleic Acids Research, Volume 19, Issue 10, 11 May 1991, Pages 2645–2653, https://doi.org/10.1093/nar/19.10.2645
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Abstract

The endothelial leukocyte adhesion molecule 1 (ELAM-1) is transiently expressed specifically on the surface of cytokine-Induced endothelial cells. We demonstrate that the transient expression of the protein is paralleled by an Increase and decrease In transcription of the ELAM-1 gene. To Identify the clsacting transcription control regions within the ELAM-1 gene that are responsible for this cytokine-induced expression, we Isolated and analyzed an ELAM-1 genomic clone containing sequences upstream of the transcription start site. We constructed a series of ELAM-1 deletion mutants linked to a reporter gene and analyzed their expression In both endothelial and nonendothelial cells. Results show that a fragment of 233 bp upstream of the transcription start site Is sufficient to confer cytokine Inducibility upon the reporter gene In both endothelial and non-endothelial cells. Further analysis defined two elements within this region that are involved In the cytokine inducibility of the ELAM-1 gene. One element lies within the −233 to −117 region, the other element represents an NF_x_B consensus binding site between nucleotides −94 to −85. Gel shift analysis reveals increased binding of an NF_x_B-like factor to this consensus sequence in extracts prepared from IL-1-induced endothelial cells. The results suggest that cytokine induction of ELAM-1 gene transcription is imparted by a combination of positive factors, one being an NF_x_B-like transcription factor, interacting with cis-acting elements within the enhancer/promoter of the gene.

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