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Papers In Press, published online ahead of print January 31, 2002
J. Biol. Chem, 10.1074/jbc.M112268200
Submitted on December 21, 2001
Revised on January 30, 2002
Accepted on January 31, 2002
-opioid receptor gene: Role of Ikaros in the stimulated transcription of mouse -opioid receptor gene in activated T cells
Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455
Corresponding Author: sunx0078{at}tc.umn.edu
-opioid receptors (DOR) present on T cells have been shown to mediate the immunomodulatory effects of endogenous and synthetic DOR agonists on T cells. Considerable evidence indicates that the transcription of DOR gene is stimulated in activated T cells, correlated with augmented expression of DOR and enhanced capacity of DOR agonists to affect the T-cell's functions. However, the molecular mechanism underlying the stimulated transcription of DOR gene in activated T cells is still unclear. In the present study, we analyzed a 1.3-kb DNA fragment immediately upstream of the translation start site (-1300 to +1 bp, with the translation start site designated as +1) of mouse DOR gene in EL-4 cells, a mouse lymphoma T cell line that exhibits enhanced expression of DOR transcripts when activated by phytohemagglutinin. Through both in vivo and in vitro experiments, we have demonstrated that increased binding activity of Ikaros at the Ikaros-binding site (-378 to -374) in the DOR promoter is essential for the stimulated transcription of DOR gene in phytohemagglutinin-activated T cells.
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