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constitutive expression

By Longchuan Bai and Juanita L. Merchant


IFNg is a pro-in¯ammatory cytokine that potentiates p53-independent apoptosis in a variety of cell types. STAT1 is the primary mediator of IFNg action. ZBP-89 is a transcription factor that binds to the G/C-rich elements and mediates p53-independent apoptosis. In this study, site-directed mutagenesis revealed that a G-rich element from +171 to +179 within the ®rst intron of the STAT1 gene is critical for optimal STAT1 promoter activity. Electrophoretic mobility shift assays and promoter analysis revealed that ZBP-89 binds directly to this STAT1 G-rich element along with Sp1 and Sp3. Reduction of ZBP-89 with siRNA attenuated both basal and IFNg-induced STAT1 expression and subsequently diminished the activation of apoptotic markers, e.g. caspase-3 and PARP. Taken together, we conclude that ZBP-89 is required for constitutive STAT1 expression and in this way contributes to the ability of cells to be activated by IFNg

Year: 2003
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