Cyclophilin J limits inflammation through the blockage of ubiquitin chain sensing.
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.
Mesh Terms:
Animals, Cercopithecus aethiops, Colitis, Cyclophilins, Dextran Sulfate, Flow Cytometry, HEK293 Cells, HeLa Cells, Humans, Lipopolysaccharides, Listeria monocytogenes, Mice, Microscopy, Confocal, NF-kappa B, Polyubiquitin, Protein Binding, RNA Interference, Sepsis, Signal Transduction, Ubiquitin, Vero Cells
Animals, Cercopithecus aethiops, Colitis, Cyclophilins, Dextran Sulfate, Flow Cytometry, HEK293 Cells, HeLa Cells, Humans, Lipopolysaccharides, Listeria monocytogenes, Mice, Microscopy, Confocal, NF-kappa B, Polyubiquitin, Protein Binding, RNA Interference, Sepsis, Signal Transduction, Ubiquitin, Vero Cells
Nat Commun
Date: Dec. 22, 2017
PubMed ID: 30348973
View in: Pubmed Google Scholar
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