Expression of glutathione S-transferase P1-1 in differentiating K562: role of GATA-1.

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Schnekenburger M, Morceau F, Duvoix A, Delhalle S, Trentesaux C, Dicato M, Diederich M

Expression of glutathione S-transferase P1-1 in differentiating K562: role of GATA-1.

Biochem Biophys Res Commun. 2003 Nov 28;311(4):815-21.

PubMed ID

14623254 [ View in PubMed

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Abstract

Glutathione S-transferase P1-1 (GSTP1-1) conjugates glutathione to electrophilic compounds and its expression is correlated to chemotherapeutic drug resistance. Results show that GSTP1-1 mRNA as well as protein expressions are increased during Aclarubicin (Acla)- and Doxorubicin (Dox)-induced erythroid differentiation of human K562 cells. In contrast, during megakaryocytic differentiation by 12-O-tetradecanoyl phorbol 13-acetate (TPA), GSTP1-1 expression decreased at both mRNA and protein levels. In order to clarify the molecular mechanisms leading to these variations, we identified a GATA sequence located at -1208 relative to the transcriptional start site of the GSTP1-1 promoter. By gel shift, competition, and supershift analyses we show here the specificity of the GATA-1 binding regulated by both anthracyclines and TPA. Altogether, these results demonstrate for the first time the implication of GATA-1 in differentiation-specific variations of GSTP1-1 expression.