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Molecular Endocrinology Vol. 5, No. 10 1498-1503
doi:10.1210/mend-5-10-1498
Copyright © 1991 by the Endocrine Society.
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Multiple Domains of the Glucocorticoid Receptor Involved in Synergism with the CACCC Box Factor(s)

Marc Muller*, Claudia Baniahmad{dagger}, Christian Kaltschmidt and Rainer Renkawitz*

Max-Planck-lnstitut für Biochemie, Genzentrum D-8033 Martinsried, Germany

Address requests for reprints to: Dr. Rainer Renkawitz, Genetisches Institut, Heinrich-Buff-Ring 58, W-6300 Giessen, Germany.

Abstract

Steroid induction of responsive genes functions through the synergistic activity of steroid receptorbinding sequences with adjacent transcription factor-binding sites. To analyze the mechanism of synergy we tested different human glucocorticoid receptor mutants for synergistic function with another transcription factor in comparison with intrinsic trans-activation obtained with a single receptor binding site (glucocorticoid response element). Multiple domains were found to be involved in synergistic activity of the glucocorticoid receptor with the CACCC box factor. Deletions within the N-terminal receptor half affected simultaneously intrinsic trans-activation and synergism. However, deletion of the hormone-binding domain mainly impaired synergism rather than intrinsic frans-activation, clearly showing that this domain synergizes by a mechanism independent of intrinsic activation. A chimeric protein where the DNA-binding domain of the glucocorticoid receptor was replaced by that of the yeast GAL4 protein also showed functional synergism. These data suggest that some of the receptor domains outside the DNA-binding domain synergize by their intrinsic trans-activating property, but the hormonebinding domain contributes to synergism by a different mechanism.

FOOTNOTES

This work was supported by grants from the Deutsche Forschungsgemeinschaft (Re 433/6–4) and the Bundesministerium fur Forschung und Technologie.

* Present address: Genetisches Institut, Justus-Liebig-Universitat, Heinrich-Buff-Ring 58, W-6300 Giessen, Germany.

{dagger} Present address: Baylor College of Medicine, Department of Cell Biology, Houston, Texas 77030.

Received for publication May 23, 1991. Revision received July 23, 1991. Accepted for publication July 26, 1991.




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