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EMBO J. 2011 Jan 5;30(1):221-31. doi: 10.1038/emboj.2010.297. Epub 2010 Nov 26.

Metalloprotease type III effectors that specifically cleave JNK and NF-κB.

Author information

  • 1Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel.

Abstract

Two major arms of the inflammatory response are the NF-κB and c-Jun N-terminal kinase (JNK) pathways. Here, we show that enteropathogenic Escherichia coli (EPEC) employs the type III secretion system to target these two signalling arms by injecting host cells with two effector proteins, NleC and NleD. We provide evidence that NleC and NleD are Zn-dependent endopeptidases that specifically clip and inactivate RelA (p65) and JNK, respectively, thus blocking NF-κB and AP-1 activation. We show that NleC and NleD co-operate and complement other EPEC effectors in accomplishing maximal inhibition of IL-8 secretion. This is a remarkable example of a pathogen using multiple effectors to manipulate systematically the host inflammatory response signalling network.

PMID:
21113130
[PubMed - indexed for MEDLINE]
PMCID:
PMC3020117
Free PMC Article
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