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Helicobacter pylori CagA activates NF‐κB by targeting TAK1 for TRAF6‐mediated Lys 63 ubiquitination
Author(s) -
Lamb Acacia,
Yang XiaoDong,
Tsang YingHung N,
Li JiangDong,
Higashi Hideaki,
Hatakeyama Masanori,
Peek Richard M,
Blanke Steven R,
Chen LinFeng
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.210
Subject(s) - caga , helicobacter pylori , proinflammatory cytokine , virulence factor , downregulation and upregulation , nfkb1 , nf κb , tumor necrosis factor alpha , transcription factor , biology , ubiquitin , pathogenicity island , transforming growth factor , signal transduction , microbiology and biotechnology , virulence , inflammation , immunology , gene , biochemistry , genetics
Helicobacter pylori ‐initiated chronic gastritis is characterized by the cag pathogenicity island‐dependent upregulation of proinflammatory cytokines, which is largely mediated by the transcription factor nuclear factor (NF)‐κB. However, the cag pathogenicity island‐encoded proteins and cellular signalling molecules that are involved in H. pylori ‐induced NF‐κB activation and inflammatory response remain unclear. Here, we show that H. pylori virulence factor CagA and host protein transforming growth factor‐β‐activated kinase 1 (TAK1) are essential for H. pylori ‐induced activation of NF‐κB. CagA physically associates with TAK1 and enhances its activity and TAK1‐induced NF‐κB activation through the tumour necrosis factor receptor‐associated factor 6‐mediated, Lys 63‐linked ubiquitination of TAK1. These findings show that polyubiquitination of TAK1 regulates the activation of NF‐κB, which in turn is used by H. pylori CagA for the H. pylori ‐induced inflammatory response.