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

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-?B) 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-? 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-?B 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-?B signaling pathway, and provide insights for understanding the homeostasis of innate immunity.

SUBMITTER: Sheng C 

PROVIDER: S-EPMC6197184 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature