Activation of the jun-D gene during treatment of human myeloid leukemia cells with 1-beta-D-arabinofuranosylcytosine.
The jun-D gene is a member of the c-jun family of early response genes that code for DNA binding proteins. The present studies demonstrate that 1-beta-D-arabinofuranosylcytosine (ara-C) increases jun-D expression in HL-525 myeloid leukemia cells. This induction by ara-C was maximal at 6 hr and transient. In contrast, ara-C had no detectable effect on the gene coding for the cAMP-responsive element binding protein 1. Nuclear run-on assays demonstrated that ara-C treatment is associated with an increased rate of jun-D transcription. The results also show that jun-D transcripts are stabilized at a posttranscriptional level in ara-C-treated cells. Taken together, these results demonstrate that ara-C induces expression of the jun-D gene and that this effect is regulated by transcriptional and posttranscriptional mechanisms.
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
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Kharbanda
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Huberman
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Kufe
D051698:Activating Transcription Factor 2; D001483:Base Sequence; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D003609:Dactinomycin / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects* / Q000235:genetics; D016758:Genes, jun / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D016350:Leucine Zippers / Q000235:genetics; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D012097:Repressor Proteins; D013268:Stimulation, Chemical; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D003561:Cytarabine; D051786:Cyclic AMP Response Element Modulator; D003609:Dactinomycin