Protein binding to the interferon response enhancer correlates with interferon induction of 2'-5'-oligoadenylate synthetase in normal and interferon-resistant Friend cells

The induction of transcription of the 2'-5'-oligoadenylate (2-5A) synthetase gene by type I (α/β) and type II (γ) interferons (INFs) has been studied in wild-type (w.t.) and IFN-resistant Friend leukemia cells (FLC). Following IFN treatment, new complexes are formed in vitro between the IFN responsive sequence (IRS) of the 2-5A synthetase gene and cellular proteins. Within minutes after IFN-α/β addition to w.t. FLC, an IRS-protein complex, designated F1, is detected, as already observed in several human cell lines. In response to IFN-γ, a novel complex, designated Fg, is observed in w.t. FLC. The Fg complex appears within 3 h, while an F1-like complex is faintly visible 10 to 24 h later. In the IFN-α/β-resistant FLC, IFN-γ induces only the Fg complex and fails to induce F1. Fg formation is correlated with the IFN-γ-induced transcription of the 2-5A synthetase gene and the appearance of the corresponding enzymatic activity in both w.t. and IFN-α/β-resistant FLC. These findings suggest that F1 and Fg represent two distinct effector complexes by which type I and type II IFNs, respectively, induce 2-5A synthetase.