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 (original) (raw)

Abstract

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 A chimeric construct consisting of the ER in which the DNA binding domain has been replaced by that of cTR alpha was able to stimulate the reporter gene. In contrast, a construct in which ER DNA binding domain has been replaced by that of gag v-erbA did not activate gene transcription.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.

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Selected References

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