Protein kinases and the proteasome join in the combinatorial control of transcription by nuclear retinoic acid receptors.
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.
Bour
Gaétan
G
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Cell Biology and Signal Transduction, BP10142/Inserm, U596/CNRS, UMR7104, Illkirch, France.
Lalevée
Sébastien
S
Rochette-Egly
Cécile
C
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
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