The antiproliferative activity of the murine interferon-inducible Ifi 200 proteins depends on the presence of two 200 amino acid domains

Interferon-inducible proteins, p200, have a modular organization consisting of one (p203) or two (p202 and p204) 200 amino acid motifs, designated as type a or b domains, The relationship between this domain organization and the anti-proliferative activity was investigated by generating a hybrid protein with the 204 a domain upstream from the 203 b domain, This 204a/203b protein inhibits the proliferation of transfected cells, delays G(0)/G(1) progression into S phase following serum restimulation, and inhibits the E2F-mediated transcriptional activity, These results demonstrate for the first time that both a and b domains are needed for inhibition of proliferation by the Ifi 200 proteins. (C) 1999 Federation of European Biochemical Societies.