Human TAF(II)55 Interacts with the Vitamin D(3) and Thyroid Hormone Receptors and with Derivatives of the Retinoid X Receptor That Have Altered Transactivation Properties

We have identified novel interactions between the human (h)TATA-binding protein-associated factor TAF(II)55 and the ligand-binding domains (LBDs) of the nuclear receptors for vitamin D(3) (VDR) and thyroid hormone (TRα). Following expression in Cos cells, hTAF(II)55 interacts with the VDR and TRα LBDs in a ligand-independent manner whereas no interactions with the retinoid X receptors (RXRs) or with other receptors were observed. Deletion mapping indicates that hTAF(II)55 interacts with a 40-amino-acid region spanning α-helices H3 to H5 of the VDR and TRα LBDs but not with the equivalent highly related region of RXRγ. TAF(II)55 also interacts with chimeric receptors in which the H3-to-H5 region of RXRγ has been replaced with that of the VDR or TRα. Furthermore, replacement of two single amino acids of the RXRγ LBD with their VDR counterparts allows the RXRγ LBD to interact with hTAF(II)55 while the corresponding double substitution allows a much stronger interaction. In transfection experiments, the single mutated RXRγ LBDs activate transcription to fivefold higher levels than wild-type RXRγ while the double mutation activates transcription to a level comparable to that observed with the VDR. There is therefore a correlation between the ability of the modified RXRs to interact with hTAF(II)55 and transactivation. These results strongly suggest that the TAF(II)55 interactions with the modified RXR LBDs modulate transcriptional activation.