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Originally published In Press as doi:10.1074/jbc.M208162200 on November 12, 2002

J. Biol. Chem., Vol. 278, Issue 4, 2304-2308, January 24, 2003
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Transcriptional Regulation of Mouse delta -Opioid Receptor Gene
IKAROS-2 AND UPSTREAM STIMULATORY FACTOR SYNERGIZE IN TRANS-ACTIVATING MOUSE delta -OPIOID RECEPTOR GENE IN T CELLS*

Ping SunDagger and Horace H. Loh

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

Considerable evidence indicates that transcription of the delta -opioid receptor (dor) gene is correlated with both the expression of DOR on T cells and the capacity of DOR agonists to modulate the immunological functions of the T cell. We previously reported that increased Ikaros (Ik) binding activity over an Ik-binding site at -378 to -374 (with the translation start site designated as +1) in the mouse dor promoter was required for the enhanced transcription of dor gene in phytohemagglutinin-activated EL-4 cells, a mouse T cell line that constitutively expresses DOR. In the present study, we have analyzed further the mouse dor promoter in EL-4 cells and have demonstrated that Ik-2 homodimers bind to the -378/-374 Ik-binding site and exerts a position-dependent trans-activation effect on the dor promoter. Moreover, an E box (-185 to -180) that binds upstream stimulatory factor is essential for the dor promoter activity in both resting and phytohemagglutinin-activated T cells. Furthermore, we have demonstrated that Ik-2 and upstream stimulatory factor synergize in trans-activating the dor promoter via the putative Ik-binding site and the E box, respectively.


* This work was supported by National Institutes of Health Grants DA-00546, DA-01583, DA-11806, and KO5-DA-70554 and by the A. and F. Stark Fund of the Minnesota Medical Foundation.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 Medical School, 6-120 Jackson Hall, 321 Church St., S. E., Minneapolis, MN 55455. Tel.: 612-626-6539; Fax: 612-625-8408; E-mail: sunx0078@tc.umn.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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