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• W3028316075 abstract "In the human promonocytic U937 cell line, pyrrolidine dithiocarbamate (PDTC) was a potent inhibitor of the nuclear factor-κB (NF-κB) signalling pathway induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). However, PDTC did not inhibit tumour necrosis factor-α (TNF-α)-induced NF-κB DNA binding activity but potentiated the effect of TNF-α on κB-dependent gene expression. The stimulatory effect of PDTC with TNF-α was not observed with an HIV-1 LTR reporter construct containing two mutated κB binding sites or with a construct with a mutation of the activating protein (AP)-2 binding site located between the two κB elements. Two distinct signalling pathways, one mediated by TPA and the other by TNF-α, were shown to interact, functionally defining a threshold important in the inhibitory or stimulatory effect of PDTC on κB-dependent gene expression. Evidence that PDTC induced AP-1 DNA binding and AP-1 reporter gene activity, raised the hypothesis that the effect of PDTC was mediated by an interaction between the AP-1 pathway and p65(RelA). Co-transfection with expression vectors for p65(RelA) and the AP-1 subunits c-Fos and c-Jun resulted in a decrease in the stimulatory effect of PDTC on HIV-1 LTR activity. Co-transfection of p65(RelA) with Tam67, a dominant negative mutant of c-Jun defective in transactivation, stimulated the effect of PDTC on HIV-1 LTR activity. Evidence that the stimulatory effect of Tam67 with PDTC was reduced with c-Jun is consistent with the hypothesis." @default.
• W3028316075 created "2020-05-29" @default.
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• W3028316075 date "1999-05-01" @default.
• W3028316075 modified "2023-09-27" @default.
• W3028316075 title "Dual Activity of Pyrrolidine Dithiocarbamate on κB-Dependent Gene Expression in U937 Cells" @default.
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• W3028316075 doi "https://doi.org/10.1016/s0898-6568(99)00022-4" @default.
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