Yersinia YopT inhibits RLH-mediated NF-κB and IRF3 signal transduction

Microbiol Immunol. 2020 Nov;64(11):768-777. doi: 10.1111/1348-0421.12842. Epub 2020 Oct 19.

Abstract

The Gram-negative bacterial pathogen Yersinia delivers six effector proteins into the host cells to block the host innate immune response. One of the effectors, YopT, is a potent cysteine protease that causes the disruption of the actin cytoskeleton to inhibit phagocytosis of the pathogen; however, its molecular mechanism and relevance to pathogenesis need further investigation. In this report, we show that RIG-I is a novel target of the YopT protein. Remarkably, YopT interacts with RIG-I and inhibits rat liver homogenate-mediated nuclear factor-κB and interferon regulatory factor-3 activation. Further studies revealed a YopT-dependent increase in the K48-polymerized ubiquitination of RIG-I. These findings suggest that YopT negatively regulates RIG-I-mediated cellular antibacterial response by targeting RIG-I.

Keywords: IFN regulatory factor-3; Yersinia YopT; nuclear factor-κB; rat liver homogenate.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • HEK293 Cells
  • Humans
  • Interferon Regulatory Factor-3 / metabolism*
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Phagocytosis
  • RAW 264.7 Cells
  • Signal Transduction / physiology*
  • Transcription Factor RelA
  • Yersinia / genetics
  • Yersinia / metabolism*

Substances

  • Bacterial Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • NF-kappa B
  • RELA protein, human
  • Transcription Factor RelA
  • YopT protein, Yersinia
  • Cysteine Endopeptidases