The E3 ubiquitin ligase tripartite motif 33 is essential for cytosolic RNA-Induced NLRP3 inflammasome activation

Leiyun Weng, Hiroki Mitoma, Coline Tricot, Musheng Bao, Ying Liu, Zhiqiang Zhang, Yong Jun Liu

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

NLRP3 is a key component of caspase-activating macromolecular protein complexes called inflammasomes. It has been found that DHX33 is a cytosolic dsRNA sensor for the NLRP3 inflammasome, which induces caspase-1-dependent production of IL-1b and IL-18 upon activation. However, how the cytosolic dsRNAs induce the interaction between DHX33 and the NLRP3 inflammasome remains unknown. In this study, we report that TRIM33, a member of the tripartite motif (TRIM) family, can bind DHX33 directly and induce DHX33 ubiquitination via the lysine 218 upon dsRNA stimulation. Knocking down of TRIM33 abolished the dsRNA-induced NLRP3 inflammasome activation in both THP-1-derived macrophages and human monocyte-derived macrophages. The ubiquitination of DHX33 by TRIM33 is lysine 63 specific and is required for the formation of the DHX33-NLRP3 inflammasome complex.

Original languageEnglish
Pages (from-to)3676-3682
Number of pages7
JournalJournal of Immunology
Volume193
Issue number7
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Inflammasomes
Ubiquitin-Protein Ligases
RNA
Ubiquitination
Lysine
Multiprotein Complexes
Caspase 1
Interleukin-18
Caspases
Macrophages

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

The E3 ubiquitin ligase tripartite motif 33 is essential for cytosolic RNA-Induced NLRP3 inflammasome activation. / Weng, Leiyun; Mitoma, Hiroki; Tricot, Coline; Bao, Musheng; Liu, Ying; Zhang, Zhiqiang; Liu, Yong Jun.

In: Journal of Immunology, Vol. 193, No. 7, 01.10.2014, p. 3676-3682.

Research output: Contribution to journalArticle

Weng, Leiyun ; Mitoma, Hiroki ; Tricot, Coline ; Bao, Musheng ; Liu, Ying ; Zhang, Zhiqiang ; Liu, Yong Jun. / The E3 ubiquitin ligase tripartite motif 33 is essential for cytosolic RNA-Induced NLRP3 inflammasome activation. In: Journal of Immunology. 2014 ; Vol. 193, No. 7. pp. 3676-3682.
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