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  • Title: 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.
    Author: Kordula T, Travis J.
    Journal: Biochem J; 1996 Feb 01; 313 ( Pt 3)(Pt 3):1019-27. PubMed ID: 8611141.
    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.
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