Characterization 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 (RXR(beta)). Binding of RAR(alpha)/RXR(beta) 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.
Lee
C H
CH
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Wei
L N
LN
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D005091:Exons; D005786:Gene Expression Regulation; D051379:Mice; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D011401:Promoter Regions, Genetic; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; C539823:Nr2c1 protein, mouse; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D011988:Receptors, Thyroid Hormone; D014212:Tretinoin