Transcription factor ZBP-89 is required for STAT1 constitutive expression

Longchuan Bai, Juanita L. Merchant

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

IFNγ is a pro-inflammatory cytokine that potentiates p53-independent apoptosis in a variety of cell types. STAT1 is the primary mediator of IFNγ 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 IFNγ-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 IFNγ.

Original languageEnglish (US)
Pages (from-to)7264-7270
Number of pages7
JournalNucleic acids research
Volume31
Issue number24
DOIs
StatePublished - Dec 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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