Antiproliferative activity of the human IFN-alpha-inducible protein IFI44

J Interferon Cytokine Res. 2007 Aug;27(8):675-80. doi: 10.1089/jir.2007.0021.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens / biosynthesis
  • Antigens / genetics
  • Antigens / metabolism
  • Antigens / physiology*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology*
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Goats
  • Growth Inhibitors / biosynthesis
  • Growth Inhibitors / genetics
  • Growth Inhibitors / physiology*
  • Guanosine Triphosphate / metabolism
  • HCT116 Cells
  • Hepatitis C / metabolism
  • Humans
  • Interferon-alpha / physiology*
  • Molecular Sequence Data
  • Protein Binding / genetics
  • Rabbits
  • Signal Transduction / genetics

Substances

  • Antigens
  • Cytoskeletal Proteins
  • Growth Inhibitors
  • IFI44 protein, human
  • Interferon-alpha
  • Guanosine Triphosphate
  • Extracellular Signal-Regulated MAP Kinases