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

作者：Sokolova Olga; Maubach Gunter; Naumann Michael^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2014, 1843(4): 715-724.

DOI：10.1016/j.bbamcr.2014.01.006

• cagPAI pathogenicity island
• I kappa B alpha
• IKK complex
• RelA
• Type 4 secretion system
• TRAF6

Helicobacter pylon 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. pylon induces the immediate early response transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappa 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-kappa B (1 kappa B alpha) kinase (IKK)-complex. IKK alpha and IKK beta, expression stabilises the regulatory IKK complex subunit NF-kappa 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 3 activated kinase I (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-kappa B signalling including transient recruitment of the 1KK-complex. Overall, our data uncover H. pylori-induced interactions and protein modifications of the 1KK complex, and its upstream regulatory factors involved in NF-kappa B activation.

• 出版日期2014-4