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J. Biol. Chem., Vol. 278, Issue 4, 2304-2308, January 24, 2003
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From the Department of Pharmacology, University of Minnesota
Medical School, Minneapolis, Minnesota 55455
Considerable evidence indicates that
transcription of the
Transcriptional Regulation of Mouse
-Opioid Receptor Gene
IKAROS-2 AND UPSTREAM STIMULATORY FACTOR SYNERGIZE IN
TRANS-ACTIVATING MOUSE
-OPIOID RECEPTOR GENE IN T CELLS*
and
-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.
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.
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