Modulation of retinoic acid response by the mouse orphan receptor Tr2-11

The biological activity of the mouse orphan receptor Tr2-ll and its truncated isoform on a DR5-type retinoic acid response element (RARE) has been examined. An alternatively spliced variant of Tr2-l 1 has been identified and designated as Tr2-l 1-L As a result of alternative splicing, Tr2-ll-t mRNA encodes a truncated receptor with the complete ligandbinding domain deleted Protein expression of T12-11 and Tr2-ll-t transcripts has been confirmed using a prokaryotic expression system. Tr2-l 1 is able to repress RA induction of an RARE-tK-luc reporter, but has no effect on the tK promoter used in this reporter. In contrast to Tr211, Tr2-ll-t exerts a dramatic stimulatory effect on RA induction of the same RARE-tK-luc reporter. Gel-shift experiments provide evidence for an interaction of Tr2-ll with DNA fragments containing this RARE. Opposite roles of Tr2-ll and Tr2-ll-t on RA signaling pathways have been suggested.