HSPBP1 facilitates cellular RLR-mediated antiviral response by inhibiting the K48-linked ubiquitination of RIG-I

Mol Immunol. 2021 Jun:134:62-71. doi: 10.1016/j.molimm.2021.03.002. Epub 2021 Mar 10.

Abstract

Retinoic acid-inducible gene I (RIG-I) plays a critical role in the recognition of intracytoplasmic viral RNA. Upon binding to the RNA of invading viruses, the activated RIG-I translocates to mitochondria, where it recruits adapter protein MAVS, causing a series of signaling cascades. In this study, we demonstrated that Hsp70 binding protein 1 (HSPBP1) promotes RIG-I-mediated signal transduction. The overexpression of HSPBP1 can increase the stability of RIG-I protein by inhibiting its K48-linked ubiquitination, and promote the activation of IRF3 and the production of IFN-β induced by Sendai virus. Knockdown and knockout of HSPBP1 leads to down-regulation of virus-induced RIG-I expression, inhibits IRF3 activation, and reduces the production of IFNB1. These results indicate that HSPBP1 positively regulates the antiviral signal pathway induced by inhibiting the K48-linked ubiquitination of RIG-I.

Keywords: HSPBP1; IFN-β; MAVS; RIG-I; RLR signaling; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • DEAD Box Protein 58 / immunology
  • DEAD Box Protein 58 / metabolism*
  • HEK293 Cells
  • Humans
  • Immunity, Innate / immunology*
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Respirovirus Infections / immunology
  • Sendai virus / immunology
  • Signal Transduction / immunology*
  • Ubiquitination

Substances

  • Adaptor Proteins, Signal Transducing
  • HSPBP1 protein, human
  • Receptors, Immunologic
  • RIGI protein, human
  • DEAD Box Protein 58