title: MEKK3 and TAK1 synergize to activate IKK complex in Helicobacter pylori infection.
abstract: Helicobacter pylori colonises the gastric epithelial cells of half of the world's population and represents a risk factor for gastric adenocarcinoma. In gastric epithelial cells H. pylori induces the immediate early response transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) and the innate immune response. We show that H. pylori induces in a type IV secretion system-dependent (T4SS) and cytotoxin associated gene A protein (CagA)-independent manner a transient activation of the inhibitor of NF-κB (IκBα) kinase (IKK)-complex. IKKα and IKKβ expression stabilises the regulatory IKK complex subunit NF-κB essential modulator (NEMO). We provide evidence for an intimate mutual control of the IKK complex by mitogen-activated protein kinase kinase kinase 3 (MEKK3) and transforming growth factor β activated kinase 1 (TAK1). TAK1 interacts transiently with the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6). Protein modifications in the TAK1 molecule, e.g. TAK1 autophosphorylation and K63-linked ubiquitinylation, administer NF-κB signalling including transient recruitment of the IKK-complex. Overall, our data uncover H. pylori-induced interactions and protein modifications of the IKK complex, and its upstream regulatory factors involved in NF-κB activation.
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, 39120 Magdeburg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Sokolova
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, 39120 Magdeburg, Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: Maubach
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, 39120 Magdeburg, Germany. Electronic address: Naumann@med.ovgu.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Naumann
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000235:genetics; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis / Q000378:metabolism; D048748:MAP Kinase Kinase Kinase 3 / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D051550:I-kappa B Kinase; D048748:MAP Kinase Kinase Kinase 3; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; D000099151:MAP Kinase Kinase Kinase 7; C491731:IKBKG protein, human; C482625:MAP3K3 protein, human
keywords: IKK complex; IκBα; RelA; TRAF6; Type 4 secretion system; cagPAI pathogenicity island