Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination.


Journal Article

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)-kappaB. However, the cag pathogenicity island-encoded proteins and cellular signalling molecules that are involved in H. pylori-induced NF-kappaB activation and inflammatory response remain unclear. Here, we show that H. pylori virulence factor CagA and host protein transforming growth factor-beta-activated kinase 1 (TAK1) are essential for H. pylori-induced activation of NF-kappaB. CagA physically associates with TAK1 and enhances its activity and TAK1-induced NF-kappaB 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-kappaB, which in turn is used by H. pylori CagA for the H. pylori-induced inflammatory response.

Full Text

Cited Authors

  • Lamb, A; Yang, X-D; Tsang, Y-HN; Li, J-D; Higashi, H; Hatakeyama, M; Peek, RM; Blanke, SR; Chen, L-F

Published Date

  • November 2009

Published In

Volume / Issue

  • 10 / 11

Start / End Page

  • 1242 - 1249

PubMed ID

  • 19820695

Pubmed Central ID

  • 19820695

Electronic International Standard Serial Number (EISSN)

  • 1469-3178

International Standard Serial Number (ISSN)

  • 1469-221X

Digital Object Identifier (DOI)

  • 10.1038/embor.2009.210


  • eng