The thyroid hormone receptor antagonizes CREB-mediated transcription.
Combinatorial regulation of transcription involves binding of transcription factors to DNA as well as protein-protein interactions between them. In this paper, we demonstrate the existence of a mutual transcriptional antagonism between the thyroid hormone receptor (TR) and the cyclic AMP response element binding protein (CREB), which involves a direct association of both transcription factors. TR inhibits transcriptional activity of CREB and represses activation of cAMP response element (CRE)-containing promoters. TR does not bind to the CRE in vitro, but in vivo the liganded receptor is tethered to the promoter through protein-protein interactions. In turn, expression of CREB reduces TR-dependent transcriptional responses. The association of TR with CREB inhibits the ability of protein kinase A to phosphorylate CREB at Ser133, and leads to a reduction in the ligand-dependent recruitment of the p160 coactivators by TR. These results indicate the existence of a transcriptional cross-talk between CREB and TR signalling pathways, which can have important functional consequences.
Méndez-Pertuz
Marinela
M
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid, Spain.
Sánchez-Pacheco
Aurora
A
Aranda
Ana
A
D000818:Animals; D050882:CREB-Binding Protein; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014284:Triiodothyronine; C012589:trichostatin A; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D017868:Cyclic AMP-Dependent Protein Kinases