Negative regulation of interferon-induced transmembrane protein 3 by SET7-mediated lysine monomethylation

J Biol Chem. 2013 Dec 6;288(49):35093-103. doi: 10.1074/jbc.M113.511949. Epub 2013 Oct 15.

Abstract

Although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-α reduced IFITM3-K88me1 levels. These findings may have important implications in the design of therapeutics targeting protein methylation against infectious diseases.

Keywords: Antiviral Agents; Antiviral Host Restriction Factors; Host Defense; Host-pathogen Interactions; IFITM3; Lysine Methylation; Post-translational Modification; Protein Methylation; SET7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Humans
  • Influenza A virus / immunology
  • Influenza A virus / pathogenicity
  • Interferon Type I / metabolism
  • Lysine / chemistry
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Methylation
  • Molecular Sequence Data
  • Protein Processing, Post-Translational
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction
  • Vero Cells
  • Vesiculovirus / immunology
  • Vesiculovirus / pathogenicity
  • Virus Diseases / immunology
  • Virus Diseases / metabolism
  • Virus Diseases / prevention & control

Substances

  • IFITM3 protein, human
  • Interferon Type I
  • Membrane Proteins
  • RNA-Binding Proteins
  • Histone-Lysine N-Methyltransferase
  • SETD7 protein, human
  • Lysine