Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication

Chunfu Wang, Michael Gale, Brian C. Keller, Hua Huang, Michael S. Brown, Joseph L. Goldstein, Jin Ye

Research output: Contribution to journalArticle

239 Scopus citations

Abstract

We recently reported that Hepatitis C virus (HCV) RNA replication requires one or more geranylgeranylated host proteins. Using a combination of [ 3H]mevalonate labeling, coimmunoprecipitation, and bioinformatic search, we identified a geranylgeranylated host protein required for HCV RNA replication. This protein, FBL2, contains an F box domain and a CAAX motif (CVIL). It forms a stable immunoprecipitable complex with the HCV nonstructural protein 5A (NS5A). The association of FBL2 with NS5A requires the CAAX motif of FBL2, but not the F box. Deletion of the F box created a dominant-negative protein that inhibited replication of HCV RNA when overexpressed in Huh7-K2040 cells; this inhibition was overcome by coexpression of NS5A. siRNA-mediated knockdown of FBL2 mRNA by 70% in Huh7-HP cells reduced HCV RNA by 65%; this reduction was overcome by expression of a cDNA encoding a wobble mutant of FBL2. The current data indicate that geranylgeranylated FBL2 binds to NS5A in a reaction crucial for HCV RNA replication.

Original languageEnglish (US)
Pages (from-to)425-434
Number of pages10
JournalMolecular cell
Volume18
Issue number4
DOIs
StatePublished - May 13 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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