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

Kobi Baruch; Lihi Gur-Arie; Chen Nadler; Simi Koby; Gal Yerushalmi; Yinon Ben-Neriah; Orli Yogev; Eitan Shaulian; Chen Guttman; Raz Zarivach; Ilan Rosenshine

doi:10.1038/emboj.2010.297

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

Kobi Baruch, Lihi Gur-Arie, Chen Nadler, Simi Koby, Gal Yerushalmi, Yinon Ben-Neriah, Orli Yogev, Eitan Shaulian, Chen Guttman, Raz Zarivach, Ilan Rosenshine

Ben-Gurion University of the Negev, The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

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.

Original language	American English
Pages (from-to)	221-231
Number of pages	11
Journal	EMBO Journal
Volume	30
Issue number	1
DOIs	https://doi.org/10.1038/emboj.2010.297
State	Published - 5 Jan 2011

Keywords

JNK
NF-κB
NleC
NleD
enteropathogenic E. coli

All Science Journal Classification (ASJC) codes

General Neuroscience
Molecular Biology
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

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10.1038/emboj.2010.297

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title = "Metalloprotease type III effectors that specifically cleave JNK and NF-κB",

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.",

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AU - Baruch, Kobi

AU - Gur-Arie, Lihi

AU - Nadler, Chen

AU - Koby, Simi

AU - Yerushalmi, Gal

AU - Ben-Neriah, Yinon

AU - Yogev, Orli

AU - Shaulian, Eitan

AU - Guttman, Chen

AU - Zarivach, Raz

AU - Rosenshine, Ilan

PY - 2011/1/5

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N2 - 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.

AB - 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.

KW - JNK

KW - NF-κB

KW - NleC

KW - NleD

KW - enteropathogenic E. coli

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DO - 10.1038/emboj.2010.297

M3 - Article

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EP - 231

JO - EMBO Journal

JF - EMBO Journal

IS - 1

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

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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