Retinoic Acid Receptors Interact Physically and Functionally with the T:G Mismatch-specific Thymine-DNA Glycosylase

The pleiotropic effects of retinoids are mediated by nuclear receptors that are activated by 9-cis- or all-trans-retinoic acid to function as ligand-dependent transcription factors. In a yeast one-hybrid screen for proteins capable of interacting with native retinoic acid receptor (RAR), we have iso...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-08, Vol.273 (33), p.20728-20736
Main Authors: Um, Soojong, Harbers, Matthias, Benecke, Arndt, Pierrat, Benoı̂t, Losson, Régine, Chambon, Pierre
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Biochemistry, Molecular Biology
Deoxyribonuclease (Pyrimidine Dimer)
Endodeoxyribonucleases - genetics
Endodeoxyribonucleases - metabolism
Guanine
Life Sciences
Mice
Molecular Sequence Data
Nucleic Acid Heteroduplexes
Protein Binding
Receptors, Retinoic Acid - metabolism
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
RNA Splicing
Sequence Homology, Amino Acid
Thymine
Transcriptional Activation
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Summary:The pleiotropic effects of retinoids are mediated by nuclear receptors that are activated by 9-cis- or all-trans-retinoic acid to function as ligand-dependent transcription factors. In a yeast one-hybrid screen for proteins capable of interacting with native retinoic acid receptor (RAR), we have isolated the T:G mismatch-specific thymine-DNA glycosylase (TDG), which initiates the repair of T:G mismatches caused by spontaneous deamination of methylated cytosines. Here, we report that TDG can interact with RAR and the retinoid X receptor (RXR) in a ligand-independent manner, both in yeast and in vitro. Mapping of the binding sites revealed interaction with a region of the ligand binding domain harboring α-helix 1 in both RAR and RXR. In transient transfection experiments, TDG potentiated transactivation by RXR from a direct repeat element spaced by one nucleotide (DR1) and by RXR/RAR heterodimers from a direct repeat element spaced by five nucleotides (DR5). In vitro, TDG enhanced RXR and RXR/RAR binding to their response elements. These data indicate that TDG is not only a repair enzyme, but could also function in the control of transcription.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.33.20728