The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA

Zhiqiang Zhang, Musheng Bao, Ning Lu, Leiyun Weng, Bin Yuan, Yong Jun Liu

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

DDX41 is a sensor of intracellular double-stranded DNA (dsDNA) in myeloid dendritic cells (mDCs) that triggers a type I interferon response via the signaling adaptor STING. We identified the E3 ligase TRIM21 as a DDX41-interacting protein and found that knockdown of or deficiency in TRIM21 resulted in enhanced type I interferon responses to intracellular dsDNA and DNA viruses. Overexpression of TRIM21 resulted in more degradation of DDX41 and less production of interferon-β (IFN-β) in response to intracellular dsDNA. The SPRY-PRY domain of TRIM21 interacted with the DEADc domain of DDX41. Lys9 and Lys115 of DDX41 were the targets of TRIM21-mediated ubiquitination. TRIM21 is therefore an interferon-inducible E3 ligase that induces the Lys48 (K48)-linked ubiquitination and degradation of DDX41 and negatively regulates the innate immune response to intracellular dsDNA.

Original languageEnglish (US)
Pages (from-to)172-178
Number of pages7
JournalNature immunology
Volume14
Issue number2
DOIs
StatePublished - Feb 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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