Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).
Nuclear retinoic acid receptors (RARs) are transcriptional regulators controlling the expression of specific subsets of genes in a ligand-dependent manner. The basic mechanism for switching on transcription of cognate target genes involves RAR binding at specific response elements and a network of 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, new roles for the N-terminal domain and the ubiquitin-proteasome system recently emerged. Moreover, the functions of RARs are not limited to the regulation of cognate target genes, as they can transrepress other gene pathways. Finally, RARs are also involved in nongenomic biological activities such as the activation of translation and of kinase cascades. Here we will review these mechanisms, focusing on how kinase signaling and the proteasome pathway cooperate to influence the dynamics of RAR transcriptional activity.
Rochette-Egly
Cécile
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Functional Genomics, INSERM U596, CNRS UMR7104, Université Louis Pasteur de Strasbourg, Strasbourg, France. cegly@igbmc.fr
Germain
Pierre
P
D002467:Cell Nucleus / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D015202:Protein Engineering / Q000379:methods*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D015533:Transcriptional Activation / Q000502:physiology*
D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid