Regulation of IL-2 gene expression and nuclear factor-90 translocation in vaccinia virus-infected cells
Nuclear factor-90 (NF-90) has been described as a regulatory subunit of a complex containing DNA-dependent protein kinase (DNA-PK), Ku, and NF-45, which are capable of binding the interleukin-2 (IL-2) enhancer region and stimulating IL-2 gene expression. Vaccinia virus (VV) infection of Jurkat cells...
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Veröffentlicht in: | Journal of interferon & cytokine research 2003-09, Vol.23 (9), p.489-500 |
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Sprache: | eng |
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Zusammenfassung: | Nuclear factor-90 (NF-90) has been described as a regulatory subunit of a complex containing DNA-dependent protein kinase (DNA-PK), Ku, and NF-45, which are capable of binding the interleukin-2 (IL-2) enhancer region and stimulating IL-2 gene expression. Vaccinia virus (VV) infection of Jurkat cells induced a nuclear factor that bound specifically to the IL-2 promoter sequence and led to the expression of the IL-2 transcript. Induction of this IL-2 promoter binding factor occurred concomitantly with the induction of NF-90 and translocation of NF-90 to the nucleus. Electrophoretic mobility supershift analysis using specific anti-NF-90 serum suggested the presence of NF-90 in the IL-2 promoter binding complex. As NF-90 can bind to double-stranded RNA (dsRNA) and be phosphorylated by the dsRNA-dependent protein kinase, PKR, we investigated whether accumulation of dsRNA in VV-infected cells could regulate IL-2 gene expression. Infection of Jurkat cells with a VV mutant that produces free dsRNA led to similar levels of induced NF-90 within the cell, but the protein remained localized within the cytosol. This mutant did not lead to the accumulation of an IL-2 promoter binding complex or to the synthesis of IL-2 mRNA. Other VV mutants that produced excess dsRNA also inhibited protein binding to the IL-2 enhancer, suggesting that the presence of viral dsRNA has a role in retaining NF-90 in the cytosol and regulating IL-2 gene expression. |
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ISSN: | 1079-9907 1557-7465 |
DOI: | 10.1089/10799900360708614 |