Nucleic Acids Research, 1990, Vol. 18, No. 15 4489-4497
© 1990
MOLECULAR BIOLOGY |
The lack of transcriptional activation of the v-erbA oncogene is in part due to a mutation present in the DNA binding domain of the protein
Laboratoire de Géenéetique Moléeculaire des Eucaryotes du CNRS, Unitée 184 de Biologie Moléeculaire et de Géenie Géenéetique de I'lNSERM, Facultée de Méedecine 11 rue Humann, 67085 Strasbourg Cedex, France
Received April 10, 1990. Revised July 5, 1990. Accepted July 5, 1990.
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 cellspecific transcription factors necessary for the response. By contrast to its cellular counterpart (cerbA/cTRA) 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 A chimeric construct consisting of the ER in which the DNA binding domain has been replaced by that of cTRa was able to stimulate the reporter gene. In contrast, a construct in which ER DNA binbing domain has been replaced by that of gag v-erbA did not activate gene transcription.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.
*Present address: Laboratoire de Gendtique Moleculaire, Faculte de Medecine X.Bichat, 16 rue Henri-Huchard, 75018 Paris, France.
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