MEKK3 and TAK1 synergize to activate IKK complex in Helicobacter pylori infection

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• 作者：Olga Sokolova ; Gunter Maubach ; Michael Naumann ; ^{Naumann@med.ovgu.de" class="auth_mail}
• 关键词：cagPAI pathogenicity island ; I魏B伪 ; IKK complex ; RelA ; Type 4 secretion system ; TRAF6
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：April, 2014
• 年：2014
• 卷：1843
• 期：4
• 页码：715-724
• 全文大小：1626 K

文摘

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-魏B) 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-魏B (I魏B伪) kinase (IKK)-complex. IKK伪 and IKK尾 expression stabilises the regulatory IKK complex subunit NF-魏B 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 尾 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-魏B 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-魏B activation.