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Regulation of 2',5'-oligoadenylate synthetase gene expression by interferons and platelet-derived growth factor.

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511.

ABSTRACT

In murine BALB/c 3T3 cell cultures, either beta interferon or platelet-derived growth factor (PDGF) enhanced expression of the 2',5'-oligoadenylate synthetase mRNA and protein. The time course of induction in response to beta interferon was similar to that in response to PDGF. Of several growth factors known to be present in clotted blood serum (i.e., epidermal growth factor, transforming growth factor beta, and PDGF), only PDGF enhanced expression of 2',5'-oligoadenylate synthetase. The linkage of an interferon response element-containing segment from the 5'-flanking region of a human or murine 2',-5'-oligoadenylate synthetase gene made a heterologous gene responsive to interferon. The expression of such a gene construct in transfected cells was also induced by PDGF. Induction by PDGF was inhibited by mono- or polyclonal antibodies to murine interferon, which suggested that induction by PDGF requires interferon. Both PDGF and interferon induced nuclear factors that bound to this interferon response element-containing segment in vitro.

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• Salzberg, S, Heller, A, Zou, J., Collart, F., Huberman, E (1996). Interferon-independent activation of (2'-5') oligoadenylate synthetase in Friend erythroleukemia cell variants exposed to HMBA. J. Cell Sci. 109: 1517-1526 [Abstract]  
• Hannigan, G., Williams, B. (1991). Signal transduction by interferon-alpha through arachidonic acid metabolism. Science 251: 204-207 [Abstract]