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PMID: 7479078 Published · ppublish English Journal Article

COUP-TF II homodimers are formed in preference to heterodimers with RXR alpha or TR beta in intact cells.

Nucleic acids research ·Vol. 23 ·No. 20 ·1995-10-25 ·Pages 4143-50

Butler AJ, Parker MG

Abstract

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses the transcriptional activity of a number of nuclear receptors, including that of retinoid receptors (RAR and RXR) and thyroid hormone receptors (TR). Since COUP-TF is capable of binding to DNA in vitro either as a homodimer or as a heterodimer with RXR or TR, it has not been possible to distinguish between competitive DNA binding and heterodimer formation as a mechanism to account for the repression. Using a two-hybrid system we have investigated the dimerisation properties of COUP-TF II in intact cells. In conditions where COUP-TF II homodimers and RXR alpha-RAR alpha heterodimers were formed we were unable to detect the formation of heterodimers between COUP-TF II and RXR alpha. Moreover, we were unable to detect an interaction between COUP-TF II and RXR alpha on DNA. Similarly COUP-TF II homodimers and RXR alpha-TR beta heterodimers are favoured over COUP-TF II-TR beta heterodimers. We conclude that the formation of functionally inactive heterodimers is unlikely to represent a general mechanism by which COUP-TF represses the transcriptional activity of nuclear receptors and favour a model in which repression is mediated by COUP-TF homodimers competing for binding to DNA.

MeSH Terms
Animals Base Sequence Binding, Competitive COUP Transcription Factors Cells, Cultured Chick Embryo DNA/metabolism DNA-Binding Proteins Fibroblasts Fungal Proteins/genetics Humans Models, Genetic Molecular Sequence Data Protein Conformation Receptors, Retinoic Acid/genetics,metabolism Receptors, Steroid Receptors, Thyroid Hormone/genetics,metabolism Recombinant Fusion Proteins/biosynthesis,metabolism Repressor Proteins/chemistry,genetics,metabolism Retinoid X Receptors Saccharomyces cerevisiae Proteins Sequence Deletion Transcription Factors/chemistry,genetics,metabolism Transcriptional Activation/drug effects,physiology Transfection Tretinoin/pharmacology
Chemicals
COUP Transcription Factors DNA-Binding Proteins Fungal Proteins GAL4 protein, S cerevisiae Receptors, Retinoic Acid Receptors, Steroid Receptors, Thyroid Hormone Recombinant Fusion Proteins Repressor Proteins Retinoid X Receptors Saccharomyces cerevisiae Proteins Transcription Factors Tretinoin DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Butler A J
Laboratory of Molecular Endocrinology, Imperial Cancer Research Fund, London, UK.
Parker M G
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44 references, click to expand
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
Published
1995-10-25
Pages
4143-50
Language
English
Region
England
NLM ID
0411011
PMCID
PMC307356
Subset
IM
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