Ubiquitination of STING at lysine 224 controls IRF3 activation

Guoxin Ni, Hiroyasu Konno, Glen N Barber

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cytosolic DNA species derived from invading microbes or leaked from the nuclear or mitochondrial compartments of the cell can trigger the induction of host defense genes by activating the endoplasmic reticulum-associated protein STING (stimulator of interferon genes). Using a mass spectrometry-based approach, we show that after association with cyclic dinucleotides, delivery of Tank-binding kinase 1 to interferon regulatory factors (IRFs), such as IRF3, relies on K63-linked ubiquitination of K224 on STING. Blocking K224 ubiquitination specifically prevented IRF3 but not nuclear factor κB activation, additionally indicating that STING trafficking is not required to stimulate the latter signaling pathway. By carrying out a limited small interfering RNA screen, we have identified MUL1 (mitochondrial E3 ubiquitin protein ligase 1) as an E3 ligase that catalyzes the ubiquitination of STING on K224. These data demonstrate the critical role of K224 ubiquitination in STING function and provide molecular insight into the mechanisms governing host defense responses.

Original languageEnglish (US)
JournalScience immunology
Volume2
Issue number11
DOIs
StatePublished - May 5 2017

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Ubiquitination
Interferons
Lysine
Genes
Ubiquitin-Protein Ligases
Interferon Regulatory Factor-1
Endoplasmic Reticulum
Small Interfering RNA
Mass Spectrometry
Phosphotransferases
DNA
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ubiquitination of STING at lysine 224 controls IRF3 activation. / Ni, Guoxin; Konno, Hiroyasu; Barber, Glen N.

In: Science immunology, Vol. 2, No. 11, 05.05.2017.

Research output: Contribution to journalArticle

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