Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level.

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Mol Cell Biol. 1993 January; 13(1): 276-288

Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level.

U M Wegenka, J Buschmann, C Lütticken, P C Heinrich and F Horn

Institute for Biochemistry, RWTH Aachen, Germany.

ABSTRACT

Interleukin-6 (IL-6) is known to be a major mediator of theacute-phase response in liver. We show here that IL-6 triggersthe rapid activation of a nuclear factor, termed acute-phaseresponse factor (APRF), both in rat liver in vivo and in humanhepatoma (HepG2) cells in vitro. APRF bound to IL-6 responseelements in the 5'-flanking regions of various acute-phase proteingenes (e.g., the alpha 2-macroglobulin, fibrinogen, and alpha1-acid glycoprotein genes). These elements contain a characteristichexanucleotide motif, CTGGGA, known to be required for the IL-6responsiveness of these genes. Analysis of the binding specificityof APRF revealed that it is different from NF-IL6 and NF-kappaB, transcription factors known to be regulated by cytokinesand involved in the transcriptional regulation of acute-phaseprotein genes. In HepG2 cells, activation of APRF was observedwithin minutes after stimulation with IL-6 or leukemia-inhibitoryfactor and did not require ongoing protein synthesis. Therefore,a preexisting inactive form of APRF is activated by a posttranslationalmechanism. We present evidence that this activation occurs inthe cytoplasm and that a phosphorylation is involved. Theseresults lead to the conclusions that APRF is an immediate targetof the IL-6 signalling cascade and is likely to play a centralrole in the transcriptional regulation of many IL-6-inducedgenes.

Mol Cell Biol. 1993 January; 13(1): 276-288

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