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 el...

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Bibliographic Details
Published in:The EMBO journal 2003-06, Vol.22 (12), p.3102-3112
Main Authors: Aranda, Ana, Méndez-Pertuz, Marinela, Sánchez-Pacheco, Aurora
Format: Article
Language:English
Subjects:
Animals
Cell Line
CREB
CREB phosphorylation
CREB-Binding Protein
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
EMBO09
EMBO37
Genes, Reporter
Humans
Hydroxamic Acids - metabolism
Nuclear Proteins - metabolism
Phosphorylation
Pituitary Gland - cytology
Pituitary Gland - metabolism
Promoter Regions, Genetic
Protein Synthesis Inhibitors - metabolism
Receptors, Thyroid Hormone - genetics
Receptors, Thyroid Hormone - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Response Elements
Signal Transduction - physiology
Thyroid
thyroid hormone receptor
Trans-Activators - metabolism
Transcription, Genetic
transcriptional repression
Triiodothyronine - metabolism
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Summary: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.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/cdg295