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KMID : 0578319940040040457
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Molecules and Cells
1994 Volume.4 No. 4 p.457 ~ p.462
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Characterization of Orphan Receptor DNA-Binding Enhacer
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Rhee, Myungchull
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Abstract
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Apolipoprotein Al regulatory protein-1 (ARP-1) binds to a regulatory element which is composed of two direct repeat motifs (site A), TGAACCCT and TGACCCCT in the apolipoprotein Al (apo Al) gene as a dimer. Because the figand of ARP-1 has not been identified, ARP-1 is classified as an orphan receptor. ARP-1 binds to various hormone response elements as a homodimer and/or a heterodimer. In most cases, they antagonize the transcriptional stimulation exerted by various nuclear receptors and their corresponding liigands. To better understand the molecular mechanism wherein ARP-1 functions as a transcriptional repressor, COS-1 cellular extract was analyzed for its effect on the DNA binding capacity of ARP-1. First, this report showed that a beat-stable protein (complex), designated orphan receptor DNA-binding enhancer (ORDE), enhanced orphan receptors´, such as ARP-1, chicken ovalbumin upstream promoter transcriptional factor (COUP-TF), and hepatocyte nuclear factor 4 (HNF4) binding to site A. Second, ORDE changed the DNA binding capacity, but neither the affinity nor the location of the band in EMSA, of ARP-1. Finally, ORDE interacted with the DNA binding domain of ARP-1. Taken together, these results suggest that a battery of orphan receptors may require ORDE to bind their cognate DNA sequences.
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