Antiproliferative activity of the human IFN-alpha-inducible protein IFI44.
The interferon-alpha (IFN-alpha)-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-alpha. 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.
Hallen
L C
LC
Roche Center for Medical Genomics, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
Burki
Y
Y
Ebeling
M
M
Broger
C
C
Siegrist
F
F
Oroszlan-Szovik
K
K
Bohrmann
B
B
Certa
U
U
Foser
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006041:Goats; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D045325:HCT116 Cells; D006526:Hepatitis C / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D011817:Rabbits; D015398:Signal Transduction / Q000235:genetics