Glenn Rosen

Publication Details

  • CHARACTERIZATION OF THE PROMOTER FOR VASCULAR CELL-ADHESION MOLECULE-1 (VCAM-1) JOURNAL OF BIOLOGICAL CHEMISTRY Iademarco, M. F., McQuillan, J. J., Rosen, G. D., Dean, D. C. 1992; 267 (23): 16323-16329

    Abstract:

    Vascular cell adhesion molecule-1 (VCAM-1) was first identified as a protein that appears on the surface of endothelial cells after exposure to inflammatory cytokines. Through interaction with its integrin counter receptor VLA-4, VCAM-1 mediates cell-cell interactions important for immune function. We have cloned and begun characterization of the promoter for the VCAM-1 gene. In a series of transfection assays into human umbilical vein endothelial cells (HUVECs), we find that silencers between positions -1.641 kilobases and -288 base pairs restrict promoter activity, and that treatment with tumor necrosis factor-alpha overcomes this inhibition and activates the promoter through two NF kappa B sites located at positions -77 and -63 base pairs of the VCAM-1 gene. This responsiveness appears cell-specific since constructs containing the VCAM-1 NF kappa B sites are not responsive to tumor necrosis factor alpha in the T-cell line Jurkat. The two VCAM-1 NF kappa B sites, which differ slightly in their sequence, form distinct complexes in gel retardation assays, suggesting that they interact with different NF kappa B-site binding proteins. The distribution of these proteins could then control activity of the NF kappa B sites. We conclude that the pattern of VCAM-1 expression in HUVECs is controlled by a combination of these silencers and NF kappa B sites.

    View details for Web of Science ID A1992JJ45800053

    View details for PubMedID 1379595

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