CANCER CELLS Orphan Nuclear Receptor Promotes Retinoid Signals

Abstract: Retinoids have multiple biological effects, including inhibition of proliferation of certain cancer cells. The retinoids often act through heterodimers of two nuclear receptors, retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Normally, the expression of RARß is enhanced through transcriptional activation in response to retinoids. However, many cancer cell lines lose this response to retinoids, even though the RAR and RXR proteins are expressed. Lin et al. now show that such retinoid-insensitive cells may be missing another nuclear receptor, the orphan receptor called COUP-TF. In cancer cell lines lacking COUP-TF, retinoid-induced expression of RARß could be restored by expression of COUP-TF. This also restored growth inhibitory and apoptotic effects of retinoic acid in these cells. COUP-TF appears to act by enhancing interaction of RAR with the transcriptional coactivator CBP, and this effect appeared to require DNA binding by COUP-TF. This mechanism of action of COUP-TF is distinct from its effects on other genes, where COUP-TF's DNA-binding activity is not required and where it has its own transactivation activity through recruitment of a different coactivator.

Lin B, Chen G.-q., Xiao D., Kolluri S.K., Cao X., Su H., Zhang X.-k. (2000) Orphan receptor COUP-TF is required for induction of retinoic acid receptor beta, growth inhibition, and apoptosis by retinoic acid in cancer cells. Mol. Cell. Biol. 20: 957-970. [Abstract] [Full Text]