THE INTERFERON-INDUCIBLE P202 PROTEIN AS A MODULATOR OF TRANSCRIPTION- INHIBITION OF NF-KAPPA-B, C-FOS, AND C-JUN ACTIVITIES

The antimicrobial, immunomodulatory, and cell growth-regulatory activi ties of the interferons are mediated by interferon-inducible proteins. One of these is p202, a nuclear protein that is encoded by the Ifi 20 2 gene from the interferon-activatable gene 200 cluster. Overexpressio n of p202 in transfected cells slows down cell proliferation. As shown earlier, p202 binds to the hypophosphorylated form of the retinoblast oma susceptibility protein. Here we report that p202 inhibits the acti vities of the NF-kappa B and the AP-1 enhancers both in transiently tr ansfected cells and in transfected stable cell lines overexpressing p2 02. Furthermore, p202 binds the NF-kappa B p50 and p65 and the AP-1 c- Fos and c-Jun transcription factors in vitro and in vivo. NF-kappa B, c-Fos, and c-Jun participate in the transcription of various cellular and viral genes, and thus p202 can modulate the expression of these ge nes in response to interferons.