E3 ubiquitin ligase Nedd4 is a key negative regulator for non-canonical inflammasome activation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02-28

AUTHORS

Qingjun Liu, Shihui Zhang, Zhongjie Sun, Xiao Guo, Hong Zhou

ABSTRACT

The non-canonical inflammasome plays important roles in endotoxic shock and pyroptosis. Murine caspase-11, corresponding to human caspase-4, is centrally located in the non-canonical inflammasome pathway, which is directly activated by cytosolic lipopolysaccharide. It has been reported that ubiquitination strictly regulates inflammatory responses. However, the role of ubiquitination in regulating the non-canonical inflammasome is little known. In this study, we show that the E3 ubiquitin ligase, Nedd4 is an important negative regulatory component of the non-canonical inflammasome pathway. Nedd4 deficiency promoted mouse death from sepsis and cell pyroptosis, resulting from non-canonical inflammasome activation. Furthermore, Nedd4 induced the K48-linked polyubiquitination and subsequent degradation of caspase-11 through the 26S proteasome. Meanwhile, caspase-11 (or caspase-4) reciprocally regulated the level of Nedd4 protein by cleavage. Thus, Nedd4 appears to have a key role in balancing the level of non-canonical inflammasome activation in response to gram-negative bacterial infection. More... »

PAGES

1-14

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41418-019-0308-7

DOI

http://dx.doi.org/10.1038/s41418-019-0308-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112439734

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30816303


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