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

Michael Schnekenburger, Franck Morceau, Annelyse Duvoix, Sylvie Delhalle, Chantal Trentesaux, Mario Dicato, Marc Diederich*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)815-821
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume311
Issue number4
DOIs
Publication statusPublished - 28 Nov 2003
Externally publishedYes

Keywords

  • Aclarubicin
  • Doxorubicin
  • Erythroid and megakaryocytic differentiation
  • GATA-1
  • GSTP1-1
  • K562
  • TPA

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