Regulation of an adaptor protein STING by Hsp90β to enhance innate immune responses against microbial infections

Cell Immunol. 2020 Oct:356:104188. doi: 10.1016/j.cellimm.2020.104188. Epub 2020 Jul 28.

Abstract

Stimulator of interferon genes (STING) plays important roles in the DNA-mediated innate immune responses. However, the regulatory mechanism of STING in terms of stabilization is not fully understood. Here, we identified the chaperone protein Hsp90s as novel STING interacting proteins. Treatment with an Hsp90 inhibitor 17-AAG and knockdown of Hsp90β but not Hsp90α reduced STING at protein level, resulted in the suppression of IFN induction in response to stimulation with cGAMP, and infections with HSV-1 and Listeria monocytogenes. Collectively, our results suggest that the control of STING protein by Hsp90β is a critical biological process in the DNA sensing pathways.

Keywords: Client protein; Hsp90; Innate immune response; Pattern recognition receptor; STING pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Viral / immunology
  • HEK293 Cells
  • HSP90 Heat-Shock Proteins / immunology*
  • HSP90 Heat-Shock Proteins / metabolism
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / immunology
  • Humans
  • Immune Evasion / immunology
  • Immunity, Innate
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • RAW 264.7 Cells
  • Signal Transduction
  • Viral Proteins / metabolism

Substances

  • DNA, Viral
  • HSP90 Heat-Shock Proteins
  • Membrane Proteins
  • STING1 protein, human
  • Sting1 protein, mouse
  • Viral Proteins