Encephalomyocarditis Virus 3C Protease Relieves TRAF Family Member-associated NF-κB Activator (TANK) Inhibitory Effect on TRAF6-mediated NF-κB Signaling through Cleavage of TANK

J Biol Chem. 2015 Nov 13;290(46):27618-32. doi: 10.1074/jbc.M115.660761. Epub 2015 Sep 11.

Abstract

TRAF family member-associated NF-κB activator (TANK) is a negative regulator of canonical NF-κB signaling in the Toll-like receptor- and B-cell receptor-mediated signaling pathways. However, functions of TANK in viral infection-mediated NF-κB activation remain unclear. Here, we reported that TANK was cleaved by encephalomyocarditis virus 3C at the 197 and 291 glutamine residues, which depends on its cysteine protease activity. In addition, encephalomyocarditis virus 3C impaired the ability of TANK to inhibit TRAF6-mediated NF-κB signaling. Interestingly, we found that several viral proteases encoded by the foot and mouth disease virus, porcine reproductive and respiratory syndrome virus, and equine arteritis virus also cleaved TANK. Our results suggest that TANK is a novel target of some viral proteases, indicating that some positive RNA viruses have evolved to utilize their major proteases to regulate NF-κB activation.

Keywords: NF-kappa B (NF-KB); cell signaling; immunology; viral protease; virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3C Viral Proteases
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Encephalomyocarditis virus / enzymology*
  • Equartevirus / enzymology
  • Foot-and-Mouth Disease Virus / enzymology
  • HEK293 Cells
  • Humans
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Porcine respiratory and reproductive syndrome virus / enzymology
  • Proteolysis*
  • TNF Receptor-Associated Factor 6 / antagonists & inhibitors
  • TNF Receptor-Associated Factor 6 / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • TANK protein, human
  • TNF Receptor-Associated Factor 6
  • Viral Proteins
  • Cysteine Endopeptidases
  • 3C Viral Proteases