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Regulation of the gene encoding glutathione S-transferase M1 (GSTM1) by the Myb oncoprotein

Abstract

The identification of Myb ‘target’ genes will not only aid in the understanding of how overexpression of Myb, or expression of activated forms of Myb, leads to cellular transformation but will also shed light on its role in normal cells. Using a combination of an estrogen-regulated Myb-transformed cell line (ERMYB) and PCR-based subtractive hybridization, we have identified the gene (GSTM1) encoding the detoxification enzyme glutathione S-transferase M1 as being transcriptionally upregulated by Myb. Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation. Mutational ana-lysis of consensus Myb-binding sites (MBS) in the promoter and electrophoretic mobility gel shift analysis indicated that one of the three potential MBS can bind Myb protein, and is the primary site involved in the regulation of this promoter by Myb.

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Acknowledgements

This work was funded in part by project grants (to TJG) from the National Health and Medical Research Council of Australia (NHMRC). PAB was the recipient of a Dawes Scholarship from the Research Fund of the Royal Adelaide Hospital. TJG was a Principal Research Fellow of the NHMRC.

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Correspondence to Thomas J Gonda.

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Bartley, P., Keough, R., Lutwyche, J. et al. Regulation of the gene encoding glutathione S-transferase M1 (GSTM1) by the Myb oncoprotein. Oncogene 22, 7570–7575 (2003). https://doi.org/10.1038/sj.onc.1207136

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