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J Biol Chem, Vol. 275, Issue 16, 11907-11914, April 21, 2000

Constitutive Activation of Retinoic Acid Receptor beta 2 Promoter by Orphan Nuclear Receptor TR2*

Li-Na WeiDagger , Xinli Hu, and Chatchai Chinpaisal||

From the Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455

The orphan nuclear receptor TR2 functions as a constitutive activator for the endogenous retinoic acid receptor beta 2 (RARbeta 2) gene expression in P19 embryonal carcinoma cells and for reporters driven by the RARbeta 2 promoter in COS-1 cells. The activation of RARbeta 2 by TR2 is mediated by the direct repeat-5 (DR5) element located in the RARbeta 2 promoter. Furthermore, cAMP exerts an enhancing effect on the activation of RARbeta 2 by TR2, which is mediated by the cAMP response element located in the 5'-flanking region of the DR5. The constitutive activation function-1 (AF-1) of TR2 is mapped to amino acid residues 10-30 in its N-terminal A segment. A direct molecular interaction occurs between CREMtau and TR2, detected by co-immunoprecipitation, which is mediated by the N-terminal AB segment of TR2. In gel mobility shift assays, TR2 competes with P19 nuclear factor binding to the RARbeta 2 promoter, and TR2 and CREMtau bind simultaneously to this DNA fragment. The role of TR2 in the early events of RA signaling process is discussed.

* This work was supported by National Institutes of Health Grant DK54733, American Cancer Society Grant RPG-99-237-CNE, and United State Department of Agriculture Grant 98-35200-6264 (to L.-N. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455. Tel.: 612-625-402; Fax: 612-625-408; E-mail: weixx009@maroon.tc.umn.edu.

|| Current address: Dept. of Pharmacology and Toxicology, Faculty of Pharmacy, Silpakorn University Nakhon Prathom, 73000.Thailand.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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