PMID: 8611141Feb 1, 1996Paper

The role of Stat and C/EBP transcription factors in the synergistic activation of rat serine protease inhibitor-3 gene by interleukin-6 and dexamethasone

The Biochemical Journal
T Kordula, J Travis

Abstract

The rat serine proteinase inhibitor 3 gene is activated by interleukin 6 (IL-6) and glucocorticoids in hepatic cells. We report here that a 147 bp promoter is sufficient for both IL-6 stimulation and glucocorticoid enhancement of IL-6 induced transcription. Within this region we identified two functional elements binding transcription factors from the C/EBP (CCAAT/enhancer binding proteins) and Stat (signal transducers and activators of transcription) families. Mutations introduced into the Stat binding site resulted in a loss of responsiveness, showing that this element is indispensable for activation. In contrast, the promoter containing the mutated C/EBP binding site was still responsive to IL-6 and glucocorticoids; however, the magnitude of the induction was decreased by 50%. The Stat binding element is an enhancer capable of conferring both responsiveness to IL-6 and partial enhancement of glucocorticoids on to a heterologous promoter. In response to IL-6 this element rapidly binds acute-phase response factor (APRF/Stat3) and, later, the protein(s) that require ongoing protein synthesis and is recognized by anti-Stat3 antibodies. In addition, long-term treatment with IL-6 results in sustained phosphorylation of APRF /Stat3.

Citations

Jan 29, 2000·Journal of Cellular Biochemistry·N CellaN E Hynes
Nov 20, 1998·Molecular and Cellular Biology·B L Burgess-Beusse, G J Darlington
Sep 14, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Wenju LuK Chul Kim
Jan 21, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Alberto ZambonBart Staels
Feb 28, 2007·The Journal of Biological Chemistry·Arianne L TheissShanthi V Sitaraman
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