Second zinc finger mutants of thyroid hormone receptor selectively preserve DNA binding and heterodimerization but eliminate transcriptional activation.

Détails

ID Serval
serval:BIB_8D35820C0C88
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Second zinc finger mutants of thyroid hormone receptor selectively preserve DNA binding and heterodimerization but eliminate transcriptional activation.
Périodique
Biochemical and biophysical research communications
Auteur⸱e⸱s
Nagaya T., Kopp P., Kitajima K., Jameson J.L., Seo H.
ISSN
0006-291X (Print)
ISSN-L
0006-291X
Statut éditorial
Publié
Date de publication
15/05/1996
Peer-reviewed
Oui
Volume
222
Numéro
2
Pages
524-530
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
Transcriptional regulation by thyroid hormone is mediated through its nuclear receptors (TRs), which bind to target responsive elements as homodimers or as heterodimers with 9-cis retinoic acid receptors (RXRs). We examined the dimerization and functional properties of TRs containing mutations in the first and second zinc finger regions of the DNA binding domain. Interestingly, a mutation (R158G) in the loop of second zinc finger, or a chimeric mutant in which the second zinc finger of the glucocorticoid receptor (GR) was substituted for that of the TR, did not form homodimer, but still bound as a heterodimer with RXR alpha. Despite the presence of heterodimer formation, these mutants were functionally inactive in transfection assays. We conclude that sequences within the loop of the second zinc finger may play an important role in stability in vivo or transcriptional activation of the TR.
Mots-clé
Amino Acid Sequence, Binding Sites, Cell Line, DNA/metabolism, DNA-Binding Proteins/biosynthesis, DNA-Binding Proteins/chemistry, DNA-Binding Proteins/metabolism, Humans, Kinetics, Luciferases/biosynthesis, Macromolecular Substances, Molecular Sequence Data, Mutagenesis, Site-Directed, Point Mutation, Promoter Regions, Genetic, Protein Structure, Secondary, Receptors, Retinoic Acid/biosynthesis, Receptors, Retinoic Acid/metabolism, Receptors, Thyroid Hormone/biosynthesis, Receptors, Thyroid Hormone/chemistry, Receptors, Thyroid Hormone/metabolism, Recombinant Fusion Proteins/biosynthesis, Recombinant Fusion Proteins/chemistry, Recombinant Fusion Proteins/metabolism, Retinoid X Receptors, Retinoids/metabolism, Transcription Factors/biosynthesis, Transcription Factors/metabolism, Transcriptional Activation, Transfection, Triiodothyronine/metabolism, Tumor Cells, Cultured, Zinc Fingers
Pubmed
Web of science
Création de la notice
30/12/2020 15:41
Dernière modification de la notice
31/12/2020 6:26
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