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Updated: Mar 25, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

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ER Adaptor SCAP Translocates and Recruits IRF3 to Perinuclear Microsome Induced by Cytosolic Microbial DNAs

Wei Chen1,2, Senlin Li1, Huansha Yu1

  • 1State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Plos Pathogens
|February 23, 2016
PubMed

Insights

The study identifies SCAP as a crucial adaptor protein in the STING signaling pathway, essential for recruiting IRF3 to combat DNA-triggered viral infections.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Signaling

Background:

  • The Stimulator of Interferon Genes (STING) pathway is vital for detecting microbial DNA and initiating antiviral responses.
  • Activation of STING leads to TBK1 kinase and IRF3 transcription factor activation.
  • The mechanism of IRF3 recruitment to the STING signalosome remains incompletely understood.

Purpose of the Study:

  • To elucidate the role of the ER adaptor SCAP in the STING signaling pathway.
  • To investigate how IRF3 is recruited to the STING signalosome.
  • To understand SCAP's contribution to host antiviral defense.

Main Methods:

  • Utilized knockdown of SCAP in cellular models.
  • Generated and analyzed Scap knockdown mice.
  • Investigated SCAP translocation using microscopy.
  • Performed protein interaction studies to map SCAP domains involved in STING and IRF3 binding.

Main Results:

  • Silencing SCAP significantly impairs STING-induced IRF3-responsive gene expression.
  • Scap knockdown mice exhibit increased susceptibility to HSV-1 infection.
  • SCAP translocates from the ER to perinuclear microsomes in a STING-dependent manner.
  • SCAP's N-terminal domain binds STING, while its C-terminal domain binds IRF3, mediating recruitment.
  • SCAP mis-localization abrogates its antiviral function.

Conclusions:

  • SCAP acts as a critical adaptor protein in the STING signaling pathway.
  • SCAP bridges STING and IRF3, facilitating the host's DNA-triggered antiviral response.
  • This study uncovers a key missing link in innate immunity against viral pathogens.

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