Cyclophilin J limits inflammation through the blockage of ubiquitin chain sensing

Chunjie Sheng, Chen Yao, Ziyang Wang, Hongyuan Chen, Yu Zhao, Dazhi Xu, Haojie Huang, Wenlin Huang, Shuai Chen

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Maintaining innate immune homeostasis is important for individual health. Npl4 zinc finger (NZF) domain-mediated ubiquitin chain sensing is reported to function in the nuclear factor-kappa B (NF-κB) signal pathway, but the regulatory mechanism remains elusive. Here we show that cyclophilin J (CYPJ), a member of the peptidylprolyl isomerase family, is induced by inflammation. CYPJ interacts with the NZF domain of transform growth factor-β activated kinase 1 binding protein 2 and 3 as well as components of the linear ubiquitin chain assembly complex to block the binding of ubiquitin-chain and negatively regulates NF-κB signaling. Mice with Cypj deficiency are susceptible to lipopolysaccharide and heat-killed Listeria monocytogenes-induced sepsis and dextran sulfate sodium-induced colitis. These findings identify CYPJ as a negative feedback regulator of the NF-κB signaling pathway, and provide insights for understanding the homeostasis of innate immunity.

Original languageEnglish (US)
Article number4381
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Sheng, C., Yao, C., Wang, Z., Chen, H., Zhao, Y., Xu, D., Huang, H., Huang, W., & Chen, S. (2018). Cyclophilin J limits inflammation through the blockage of ubiquitin chain sensing. Nature Communications, 9(1), [4381]. https://doi.org/10.1038/s41467-018-06756-3