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Nat Commun. 2018 Oct 22;9(1):4381. doi: 10.1038/s41467-018-06756-3.

Cyclophilin J limits inflammation through the blockage of ubiquitin chain sensing.

Author information

1
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 510060, Guangzhou, Guangdong, China.
2
Department of Pathogen Biology and Immunology, School of Basic Course, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China.
3
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.
4
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 510060, Guangzhou, Guangdong, China. shuaichen2010@hotmail.com.

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.

PMID:
30348973
PMCID:
PMC6197184
DOI:
10.1038/s41467-018-06756-3
[Indexed for MEDLINE]
Free PMC Article

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