Published 2017
| Version v1
Journal article
Open
Bacterial effector NleL promotes enterohemorrhagic E. coli-induced attaching and effacing lesions by ubiquitylating and inactivating JNK
Creators
- 1. Chinese Academy of Sciences
- 2. Donghua University
- 3. University of California, Los Angeles
- 4. Jilin University
- 5. University of Chicago
- 6. Northeast Agricultural University
- 7. National Institute of Biological Sciences
Description
As a major diarrheagenic human pathogen, enterohemorrhagic Escherichia coli (EHEC) produce attaching and effacing (A/E) lesions, characterized by the formation of actin pedestals, on mammalian cells. A bacterial T3SS effector NleL from EHEC O157:H7 was recently shown to be a HECT-like E3 ligase in vitro, but its biological functions and host targets remain elusive. Here, we report that NleL is required to effectively promote EHEC-induced A/E lesions and bacterial infection. Furthermore, human c-Jun NH2-terminal kinases (JNKs) were identified as primary substrates of NleL. NleL-induced JNK ubiquitylation, particularly mono-ubiquitylation at the Lys 68 residue of JNK, impairs JNK's interaction with an upstream kinase MKK7, thus disrupting JNK phosphorylation and activation. This subsequently suppresses the transcriptional activity of activator protein-1 (AP-1), which modulates the formation of the EHEC-induced actin pedestals. Moreover, JNK knockdown or inhibition in host cells complements NleL deficiency in EHEC infection. Thus, we demonstrate that the effector protein NleL enhances the ability of EHEC to infect host cells by targeting host JNK, and elucidate an inhibitory role of ubiquitylation in regulating JNK phosphorylation.
Data availability
All relevant data are within the paper and its Supporting Information files.Files
journal.ppat.1006534.pdf
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(27.5 MB)
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Additional details
Identifiers
- DOI
- 10.1371/journal.ppat.1006534
- Other
- oai:uchicago.tind.io:6634
Funding
- Chinese Academy of Sciences
- Strategic Priority Research Program
- National Science Foundation of China
- award for national outstanding young scientists
- National Science Foundation of China
- award for national outstanding young scientists
- National Science Foundation of China
- award for national outstanding young scientists
- Ministry of Science and Technology, China
- 2012CB910800
- Ministry of Science and Technology, China
- 2013CB910900
- National Institutes of Health
- F30CA183528
- Shanghai Institute of Organic Chemistry
- Chinese Academy of Sciences
- Instrument Developing Project