PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4

Nat Immunol. 2009 Dec;10(12):1300-8. doi: 10.1038/ni.1815. Epub 2009 Nov 1.


MAVS is critical in innate antiviral immunity as the sole adaptor for RIG-I-like helicases. MAVS regulation is essential for the prevention of excessive harmful immune responses. Here we identify PCBP2 as a negative regulator in MAVS-mediated signaling. Overexpression of PCBP2 abrogated cellular responses to viral infection, whereas knockdown of PCBP2 exerted the opposite effect. PCBP2 was induced after viral infection, and its interaction with MAVS led to proteasomal degradation of MAVS. PCBP2 recruited the HECT domain-containing E3 ligase AIP4 to polyubiquitinate and degrade MAVS. MAVS was degraded after viral infection in wild-type mouse embryonic fibroblasts but remained stable in AIP4-deficient (Itch(-/-)) mouse embryonic fibroblasts, coupled with greatly exaggerated and prolonged antiviral responses. The PCBP2-AIP4 axis defines a new signaling cascade for MAVS degradation and 'fine tuning' of antiviral innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line
  • Humans
  • Immunity, Innate*
  • Mice
  • Mice, Knockout
  • Newcastle disease virus / immunology
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Repressor Proteins / metabolism*
  • Sendai virus / immunology
  • Signal Transduction
  • Ubiquitin-Protein Ligases / deficiency
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / immunology
  • Ubiquitin-Protein Ligases / metabolism*
  • Vesiculovirus / immunology


  • Adaptor Proteins, Signal Transducing
  • IPS-1 protein, mouse
  • MAVS protein, human
  • PCBP2 protein, human
  • Pcbp2 protein, mouse
  • RNA-Binding Proteins
  • Repressor Proteins
  • ITCH protein, human
  • Itch protein, mouse
  • Ubiquitin-Protein Ligases