Expression of glutathione S-transferase P1-1 in differentiating K562: role of GATA-1.
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.
Schnekenburger
Michael
M
Laboratoire de Recherche sur le Cancer et les Maladies du Sang (RCMS), Centre Universitaire de Luxembourg, Bâtiment des Sciences, 162A, avenue de la Fai;encerie, L-1511, Luxembourg, Luxembourg.
Morceau
Franck
F
Duvoix
Annelyse
A
Delhalle
Sylvie
S
Trentesaux
Chantal
C
Dicato
Mario
M
Diederich
Marc
M
D015250:Aclarubicin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004317:Doxorubicin; D041905:Erythroid Cells / Q000187:drug effects / Q000473:pathology*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D020014:K562 Cells; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D007527:Isoenzymes; D014157:Transcription Factors; D015250:Aclarubicin; D004317:Doxorubicin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D013755:Tetradecanoylphorbol Acetate