Fiche publication
Date publication
août 1990
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel
Tous les auteurs :
de Verneuil H, Metzger D
Lien Pubmed
Résumé
Using a transient co-transfection system we have demonstrated that response elements for estrogen (ER), thyroid hormone (TR) and retinoic acid receptors (RAR) are closely related. Thyroid hormone-induced activation of transcription was observed in CV1 cells and not in HeLa cells, suggesting the existence of cell-specific transcription factors necessary for the response. By contrast to its cellular counterpart (c-erbA/cTR alpha) the oncogene protein gag v-erbA is unable to activate gene transcription from different response elements derived from the rat growth hormone (rGH) gene promoter. A chimeric construct consisting of the ER in which the DNA binding domain has been replaced by that of cTR alpha was able to stimulate the reporter gene. In contrast, a construct in which ER DNA binding domain has been replaced by that of gag v-erbA did not activate gene transcription. These results lead us to the conclusion that the mutated DNA binding domain of v-erbA is in part responsible for the lack of transcriptional activation and in repression of gene expression. This is due in large part to the Gly73----Ser mutation which corresponds to the position of one of the three discriminating amino acids that are thought to interact with a specific base of the response element.
Mots clés
Amino Acid Sequence, Base Sequence, Binding, Competitive, Carrier Proteins, genetics, Cell Line, DNA, genetics, Gene Expression Regulation, Growth Hormone, genetics, HeLa Cells, Humans, Molecular Sequence Data, Mutation, Oncogene Proteins v-erbA, Promoter Regions, Genetic, Receptors, Estrogen, genetics, Receptors, Retinoic Acid, Receptors, Thyroid Hormone, genetics, Repressor Proteins, metabolism, Retroviridae Proteins, Oncogenic, genetics, Sequence Homology, Nucleic Acid, Transcription Factors, genetics, Transcription, Genetic, Transfection
Référence
Nucleic Acids Res.. 1990 Aug;18(15):4489-97
