title: Protein kinases and the proteasome join in the combinatorial control of transcription by nuclear retinoic acid receptors.
abstract: Nuclear retinoic acid receptors (RARs) are transcriptional transregulators that control the expression of specific subsets of genes in a ligand-dependent manner. The basic mechanism for switching on gene transcription by agonist-liganded RARs involves their binding at specific response elements located in target genes. It also involves interactions with coregulatory protein complexes, the assembly of which is directed by the C-terminal ligand-binding domain of RARs. In addition to this scenario, several recent studies highlighted a fundamental role for the N-terminal domain in the transcriptional activity of RARs, following phosphorylation by the CDK7 kinase of the general transcription factor TFIIH and by p38MAPK. It has also emerged that the ubiquitin-proteasome system has a key role in RAR-mediated transcription. Here, we review new insights into how N-terminal domain and the proteasome pathway can influence the dynamics of RAR transcriptional activity.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Cell Biology and Signal Transduction, BP10142/Inserm, U596/CNRS, UMR7104, Illkirch, France.
authors.forename: Gaétan
authors.initials: G
authors.lastname: Bour
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lalevée
authors.forename: Cécile
authors.initials: C
authors.lastname: Rochette-Egly
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008958:Models, Molecular; D009124:Muscle Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000378:metabolism; D014158:Transcription, Genetic; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D009124:Muscle Proteins; D018168:Receptors, Retinoic Acid; C486523:SORBS3 protein, human; D051758:Transcription Factor TFIIH; D011494:Protein Kinases; D018844:Cyclin-Dependent Kinases; D046988:Proteasome Endopeptidase Complex; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human