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http://purl.uniprot.org/citations/22158122http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22158122http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22158122http://www.w3.org/2000/01/rdf-schema#comment"NF-κB is crucial for innate immune defence against microbial infection. Inhibition of NF-κB signalling has been observed with various bacterial infections. The NF-κB pathway critically requires multiple ubiquitin-chain signals of different natures. The question of whether ubiquitin-chain signalling and its specificity in NF-κB activation are regulated during infection, and how this regulation takes place, has not been explored. Here we show that human TAB2 and TAB3, ubiquitin-chain sensory proteins involved in NF-κB signalling, are directly inactivated by enteropathogenic Escherichia coli NleE, a conserved bacterial type-III-secreted effector responsible for blocking host NF-κB signalling. NleE harboured an unprecedented S-adenosyl-l-methionine-dependent methyltransferase activity that specifically modified a zinc-coordinating cysteine in the Npl4 zinc finger (NZF) domains in TAB2 and TAB3. Cysteine-methylated TAB2-NZF and TAB3-NZF (truncated proteins only comprising the NZF domain) lost the zinc ion as well as the ubiquitin-chain binding activity. Ectopically expressed or type-III-secretion-system-delivered NleE methylated TAB2 and TAB3 in host cells and diminished their ubiquitin-chain binding activity. Replacement of the NZF domain of TAB3 with the NleE methylation-insensitive Npl4 NZF domain resulted in NleE-resistant NF-κB activation. Given the prevalence of zinc-finger motifs and activation of cysteine thiol by zinc binding, methylation of zinc-finger cysteine might regulate other eukaryotic pathways in addition to NF-κB signalling."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.org/dc/terms/identifier"doi:10.1038/nature10690"xsd:string
http://purl.uniprot.org/citations/22158122http://purl.org/dc/terms/identifier"doi:10.1038/nature10690"xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Chen S."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Chen S."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Ge J."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Ge J."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Lu Q."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Lu Q."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Liu L."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Liu L."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Xu H."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Xu H."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Zhang L."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Zhang L."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Zhou Y."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Zhou Y."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Shao F."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Shao F."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Hu L."xsd:string
http://purl.uniprot.org/citations/22158122http://purl.uniprot.org/core/author"Hu L."xsd:string