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- W2024667875 abstract "Abstract: The present study examines genetic mechanism(s) possibly involved in the observed 3′‐azido‐3′‐deoxythymidine (AZT)‐induced inhibition of globin gene transcription by evaluating the direct phenotypic erythroid effects of AZT on erythroid‐specific transcription factors which regulate globin gene promoters. In vitro binding of GATA‐1 or NFE‐2 to its consensus sequence was decreased in the presence of AZT reaching a maximum inhibition as early as 24 h after AZT treatment. Nuclear extracts from butyric acid‐induced K562 cells treated with an IC 50 concentration of AZT exhibited a decrease in GATA‐1 and NFE‐2 binding by approximately 30% and 35%. In contrast, 2′,3′‐dideoxycytidine which inhibits cell growth without affecting hemoglobin synthesis, had no effect on binding of GATA‐1 and NFE‐2 factors. Northern blot analysis revealed a 25% decrease by AZT in GATA‐1 mRNA steady‐state levels at 24 h and this inhibitory effect was maintained until 72 h after drug addition. A similar decrease in NFE‐2 mRNA steady‐state levels was observed at 72 h after AZT treatment. This study suggests that AZT inhibition of erythroid differentiation is subsequent to a decrease of nuclear factors gene expression which affect their DNA binding." @default.
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- W2024667875 date "1996-01-02" @default.
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- W2024667875 title "3‘-Azido- 3’-deoxythymidine inhibits erythroid-specific transcription factors in human erythroid K562 leukemia cells" @default.
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- W2024667875 doi "https://doi.org/10.1111/j.1600-0609.1996.tb00296.x" @default.
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