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• W296088407 endingPage "734" @default.
• W296088407 startingPage "728" @default.
• W296088407 abstract "Abstract Previous studies have shown that 1-beta-D-arabinofuranosylcytosine (ara- C) induces transcription of the c-jun immediate early response gene in human myeloid leukemia cells. The present work has examined the mechanisms responsible for this effect. Deleted forms of the c-jun promoter were linked to the chloramphenicol acetyltransferase (CAT) gene and transfected into KG-1 cells. The results demonstrate that ara- C-induced c-jun transcription is mediated by an element between positions -74 and -20 upstream to the start site. Electrophoretic mobility shift assays with the fragment f(-74/-20) showed an increase in binding with nuclear proteins from ara-C-treated cells as compared with untreated cells. Competition with an oligonucleotide containing the AP-1 consensus sequence indicated that ara-C stimulates binding of nuclear proteins at the AP-1 site in the c-jun promoter. These findings were confirmed in other gel shift studies with the collagenase enhancer AP-1 consensus sequence and with a DNA fragment containing an altered AP-1 site. The binding of JUN/AP-1 was maximal at 1 hour of ara-C treatment and decreased to baseline levels at 12 hours. The finding that ara-C induces AP-1 binding in the absence of protein synthesis indicated that this agent activates already synthesized JUN/AP-1. To confirm these findings, the AP-1 consensus sequence was introduced 5′ to the heterologous SV40 promoter. The results show that AP-1 enhances SV40 promoter activity in ara-C-treated cells. Taken together, these findings indicate that: (1) enhancement of JUN/AP-1 activity in ara-C- treated cells involves a posttranslational modification of JUN/AP-1; and (2) binding of activated JUN/AP-1 to the AP-1 site in the c-jun promoter confers ara-C inducibility of this gene." @default.
• W296088407 created "2016-06-24" @default.
• W296088407 creator A5026112476 @default.
• W296088407 creator A5061442756 @default.
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• W296088407 date "1992-02-01" @default.
• W296088407 modified "2023-10-17" @default.
• W296088407 title "Activation of the AP-1 transcription factor by arabinofuranosylcytosine in myeloid leukemia cells" @default.
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• W296088407 doi "https://doi.org/10.1182/blood.v79.3.728.728" @default.
• W296088407 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1310062" @default.
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