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Nucleic Acids Research, 2003, Vol. 31, No. 24 7264-7270
© 2003 Oxford University Press

Article

Transcription factor ZBP-89 is required for STAT1 constitutive expression

Longchuan Bai1 and Juanita L. Merchant*,1,2

1 Department of Internal Medicine and 2 Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA

*To whom correspondence should be addressed. Tel: +1 734 647 2944; Fax: +1 734 763 4686; Email: merchanj{at}umich.edu

IFN{gamma} is a pro-inflammatory cytokine that potentiates p53-independent apoptosis in a variety of cell types. STAT1 is the primary mediator of IFN{gamma} 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 first 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 IFN{gamma}-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 IFN{gamma}.


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