Antiproliferative Activity of the Human IFN-α-Inducible Protein IFI44

The interferon-α (IFN-α)-inducible protein IFI44 is associated with hepatitis C virus (HCV) infection, and its function is unknown. We show here in two human melanoma cell lines (ME15 and D10) that transcription starts 4 h after induction, and peak protein levels are reached 24 h after stimulation. We show by immunofluorescence, viral overexpression, and cellular fractionation that IFI44 is a cytoplasmic protein. Overexpression of IFI44 cDNA induces an antiproliferative state in vitro, even in cells that are not responsive to IFN-α. IFI44 contains a perfect GTP binding site but has no homology to known GTPases or G proteins. Based on these results, we propose a model in which IFI44 binds intracellular GTP, and this depletion abolishes extracellular signal-regulated kinase (ERK) signaling and results finally in cell cycle arrest.