Characterisation of the mouse nuclear orphan receptor TR2-11 gene promoter and its potential role in retinoic acid-induced P19 apoptosis

The complete mouse orphan nuclear receptor TR2-11 gene structure and its 5'-untranscribed region were characterized. This gene contains 14 exons, with the first exon encoding only the 5'-untranslated sequence. The regulatory region of this gene was characterized by using reporter assays that define the minimal promoter activity in a sequence 212 nucleotides upstream from the translation initiation site. Furthermore, it was concluded that splicing of intron 1 is required for efficient promoter activity. Reporters driven by this promoter were induced by retinoic acid (RA) in COS-1 cells supplied with exogenous retinoic acid receptor-alpha (RAR(alpha)) and retinoid receptor X-beta (RXRbeta). Binding of RAR(alpha)/RXRbeta to the minimal promoter region was demonstrated in gel retardation assays. In P19 cells, both the endogenous TR2-11 gene and the reporters driven by this promoter were induced by RA in a protein synthesis-independent manner, and overexpression of TR2-11 protein resulted in cellular apoptosis in the absence of RA. The regulation of TR2-11 by RA and the implication of TR2 up-regulation in P19 cellular apoptosis are discussed. BIOCHEM PHARMACOL 60;1:127-136, 2000. (C) 2000 Elsevier Science Inc.