INTERFERON-RESISTANT DAUDI CELLS ARE DEFICIENT IN INTERFERON-ALPHA-INDUCED ISGF3-ALPHA ACTIVATION, BUT REMAIN SENSITIVE TO THE INTERFERON-ALPHA-INDUCED INCREASE IN ISGF3-GAMMA CONTENT

Low levels of the transcription factor ISGF3alpha were detected in the cytoplasm and nucleus of untreated Daudi cells, which increased marke dly following interferon (IFN) treatment. In contrast no ISGF3alpha wa s detected in an IFN-resistant clone of Daudi cells, DIF8, and only lo w levels were detected in these cells after IFN-alpha treatment. High levels of ISGF3 were produced in vitro, however, by the addition of IS GF3alpha to extracts of IFN-treated DIF8 cells, indicating that IFN is unable to produce substantial amounts of functional ISGF3alpha in DIF 8 cells. A second clone of IFN-resistant Daudi cells, DIF3, also exhib ited defective ISGF3alpha production, which was restored to normal in the subclone DIF3REV5 that had reverted to high IFN sensitivity. Thus, the antiproliferative effect of IFN on Daudi cells and derived clones is closely related to the level of ISGF3 present in the nucleus of th ese cells. IFN-alpha, however, also enhances the content of ISGF3gamma in IFN-resistant cells as well as certain proteins of unknown functio n, raising the possibility that a second pathway of IFN-alpha signal t ransduction, distinct from the ISGF3 pathway, remains functional in bo th DIF8 and DIF3 cells.