The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation.
Transcriptional coactivators are involved in gene activation by nuclear hormone receptors. The receptor-associated coactivator 3 (RAC3) was recently identified to be highly related to the steroid receptor coactivator-1 and transcriptional intermediate factor 2, thereby establishing a novel family of nuclear receptor coactivators. In this study, we identified a RAC3 fragment containing three LXXLL motifs conserved among this family, which is sufficient to mediate nuclear receptor interaction in vivo and in vitro. Point mutations that disrupt ligand-dependent activation function of the receptor inhibited the interaction. We found that a 162-amino acid fragment of RAC3 conferred transcriptional activation and recruited the CREB-binding protein and that three distinct LXXLL motifs mediated the transcriptional activation. A trimeric far Western analysis demonstrated the formation of a ternary complex containing CREB-binding protein, RAC3, and the receptor. In addition, we showed that RAC3, transcriptional intermediate factor 2, and steroid receptor coactivator-1 are expressed in specific tissues and cancer cells and that RAC3 transcript is directly up-regulated by retinoid treatment. These results suggest that RAC3 may contribute to amplified transcriptional responses through both recruitment of additional coactivators and autoregulation by the receptor-coactivator complex.
Li
H
H
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0126, USA.
Chen
J D
JD
D000818:Animals; D050882:CREB-Binding Protein; D002460:Cell Line; D002522:Chlorocebus aethiops; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D010446:Peptide Fragments / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection / Q000235:genetics
D009687:Nuclear Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011987:Receptors, Steroid; D012176:Retinoids; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3