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Metalloprotease type III effectors that specifically cleave JNK and NF‐κB
Author(s) -
Baruch Kobi,
GurArie Lihi,
Nadler Chen,
Koby Simi,
Yerushalmi Gal,
BenNeriah Yi,
Yogev Orli,
Shaulian Eitan,
Guttman Chen,
Zarivach Raz,
Rosenshine Ilan
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.297
Subject(s) - biology , metalloproteinase , cleave , effector , microbiology and biotechnology , matrix metalloproteinase , genetics , enzyme , biochemistry
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.