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.
Mesh Terms:
Animals, CREB-Binding Protein, Cell Line, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Genes, Reporter, Humans, Hydroxamic Acids, Nuclear Proteins, Phosphorylation, Pituitary Gland, Promoter Regions, Genetic, Protein Synthesis Inhibitors, Receptors, Thyroid Hormone, Recombinant Fusion Proteins, Response Elements, Signal Transduction, Trans-Activators, Transcription, Genetic, Triiodothyronine
EMBO J.
Date: Jun. 16, 2003
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