LIM protein Ajuba functions as a nuclear receptor corepressor and negatively regulates retinoic acid signaling

摘要: Corepressors play an essential role in nuclear receptor-mediated transcriptional repression. In general, corepressors directly bind to receptors via CoRNR boxes (L/I-X-X-I/V-I) the absence of ligand and appear act as scaffolds further recruit chromatin remodeling complexes specific target genes. Here, we describe identification multiple LIM domain protein Ajuba a unique corepressor for subset hormone receptors. contains functional nuclear-receptor interacting motifs selectively interacts with retinoic acid (RARs) rexinoid receptor (RXRs) subtypes ligand-dependent manner. Simultaneous mutation these abolishes RAR binding concomitantly leads loss repression on RARE reporter P19 cells depleted are highly sensitized all-trans (atRA)-induced transcription differentiation. atRA, can be readily found at control elements endogenous Stimulation atRA results dissociation from regions. Moreover, observed that coexpression known partner Prmt5 (protein arginine methyltransferase-5) inhibited Ajuba/RAR interaction. The high-affinity Ajuba-RAR/RXR interaction site overlaps region responsible Ajuba/Prmt5 binding, thus appears mutually exclusive, providing potential mechanism observations. Identification sheds new light mechanisms provides developing more effective therapeutics modulate this important pathway.