The orphan nuclear receptor TR2 functions as a constitutive activator for the endogenous retinoic acid receptor ␤2 (RAR ␤2 ) gene expression in P19 embryonal carcinoma cells and for reporters driven by the RAR ␤2 promoter in COS-1 cells. The activation of RAR ␤2 by TR2 is mediated by the direct repeat-5 (DR5) element located in the RAR ␤2 promoter. Furthermore, cAMP exerts an enhancing effect on the activation of RAR ␤2 by TR2, which is mediated by the cAMP response element located in the

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... king 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 CREM 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 ␤2 promoter, and TR2 and CREM bind simultaneously to this DNA fragment. The role of TR2 in the early events of RA signaling process is discussed.