ArticlePLoS pathogens2017
Bacterial effector NleL promotes enterohemorrhagic E. coli-induced attaching and effacing lesions by ubiquitylating and inactivating JNK.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Manipulation of nonclassical ubiquitin signaling by pathogenic bacteria.Current opinion in microbiology · 2026Review
- Discerning dangerous gain of function: most gain of function (GoF) research does not involve infectious microbes.Frontiers in bioengineering and biotechnology · 2026Review
- Article
- Why put yourself on a pedestal? The pathogenic role of the A/E pedestal.Infection and immunity · 2024Review
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Bacterial ligases reveal fundamental principles of polyubiquitin specificity.Molecular cell · 2023Article
- Ubiquitin-Dependent and Independent Proteasomal Degradation in Host-Pathogen Interactions.Molecules (Basel, Switzerland) · 2023Review
- Ubiquitin-targeted bacterial effectors: rule breakers of the ubiquitin system.The EMBO journal · 2023Review
- Bacterial mimicry of eukaryotic HECT ubiquitin ligation.bioRxiv : the preprint server for biology · 2023Article
- The NEL Family of Bacterial E3 Ubiquitin Ligases.International journal of molecular sciences · 2022Review
- Categorizing Sequences of Concern by Function To Better Assess Mechanisms of Microbial Pathogenesis.Infection and immunity · 2022Review
- Structural basis for specific recognition of K6-linked polyubiquitin chains by the TAB2 NZF domain.Biophysical journal · 2021Article
- Current Understanding of the Structure and Function of Pentapeptide Repeat Proteins.Biomolecules · 2021Review
- Bacteria make surgical strikes on host ubiquitin signaling.PLoS pathogens · 2021Review
- Ubiquitination as an Important Host-Immune Response Strategy in Penaeid Shrimp: Inferences From Other Species.Frontiers in immunology · 2021Review
- Interesting Biochemistries in the Structure and Function of Bacterial Effectors.Frontiers in cellular and infection microbiology · 2021Review
- Enterohemorrhagic E. coli effector NleL disrupts host NF-κB signaling by targeting multiple host proteins.Journal of molecular cell biology · 2020Article
- Modification of the host ubiquitome by bacterial enzymes.Microbiological research · 2020Review
- Programmed Cell Death in the Evolutionary Race against Bacterial Virulence Factors.Cold Spring Harbor perspectives in biology · 2020Review
- Divergence of Legionella Effectors Reversing Conventional and Unconventional Ubiquitination.Frontiers in cellular and infection microbiology · 2020Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.