Constitutive activation of retinoic acid receptor β2 promoter by orphan nuclear receptor TR2

The orphan nuclear receptor TR2 functions as a constitutive activator for the endogenous retinoic acid receptor β2 (RAR(β2)) gene expression in P19 embryonal carcinoma cells and for reporters driven by the RAR(β2) promoter in COS-1 cells. The activation of RAR(β2) by TR2 is mediated by the direct repeat-5 (DR5) element located in the RAR(β2) promoter. Furthermore, cAMP exerts an enhancing effect on the activation of RAR(β2) 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 CREMτ 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 RAR(β2) promoter, and TR2 and CREMτ bind simultaneously to this DNA fragment. The role of TR2 in the early events of RA signaling process is discussed.