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.
ASJC Scopus subject areas
- Molecular Biology