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J Interferon Cytokine Res. 2007 Aug;27(8):675-80.

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

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  • 1Roche Center for Medical Genomics, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.

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.

PMID:
17784819
DOI:
10.1089/jir.2007.0021
[PubMed - indexed for MEDLINE]
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