Abstract
Acetylation modification regulates the functions of histone and nonhistone proteins, including transcriptional activity, protein interaction, and subcellular localization. Although many nuclear receptors have been shown to be modified by acetylation, whether retinoid X receptors (RXRs) are acetylated and how the acetylation is regulated remains unknown. Here, we provide the first evidence of RXRα acetylation by p300 on lysine 145. Acetylation of RXRα by p300 facilitated its DNA binding and subsequently increased its transcriptional activity. Furthermore, we discovered that TR3, an orphan receptor, exerted a negative regulation on p300-induced RXRα acetylation. TR3 significantly reduced the p300-induced RXRα acetylation and transcriptional activity, and such inhibition required the interaction of TR3 with RXRα. Binding of TR3 to RXRα resulted in the sequestration of RXRα from p300. 9-cis retinoic acid, a ligand for RXRα, enhanced the association of RXRα with TR3, rather than acetylation of RXRα by p300. Biological function analysis revealed that the mitogenic activity of RXRα stimulated by p300 was acetylation dependent and could be repressed by TR3. Upon the treatment of 9-cis retinoic acid, RXRα was translocated with TR3 from the nucleus to the mitochondria, and apoptosis was induced. Taken together, our data demonstrate the distinct regulatory mechanisms of p300 and TR3 on RXRα acetylation and reveal a previously unrecognized role for orphan receptor in the transcriptional control of retinoid receptors.
Widespread translational remodeling during human neuronal differentiation
