DOI: 10.1038/embor.2009.210. <i>Helicobacter pylori</i> CagA activates NF‐κB by targeting TAK1 for TRAF6‐mediated Lys 63 ubiquitination

Helicobacter pylori CagA activates NF‐κB by targeting TAK1 for TRAF6‐mediated Lys 63 ubiquitination

10.1038/embor.2009.210

Crossref journal-article

Springer Science and Business Media LLC

EMBO reports (297)

Abstract

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.

Bibliography

Lamb, A., Yang, X., Tsang, Y. N., Li, J., Higashi, H., Hatakeyama, M., Peek, R. M., Blanke, S. R., & Chen, L. (2009). Helicobacter pylori CagA activates NFâÎºB by targeting TAK1 for TRAF6âmediated Lys 63 ubiquitination. EMBO Reports, 10(11), 1242â1249. Portico.

Authors 9

Acacia Lamb (first)
Xiao‐Dong Yang (additional)
Ying‐Hung N Tsang (additional)
Jiang‐Dong Li (additional)
Hideaki Higashi (additional)
Masanori Hatakeyama (additional)
Richard M Peek (additional)
Steven R Blanke (additional)
Lin‐Feng Chen (additional)

References 32 Referenced 152

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Dates

Type	When
Created	15 years, 10 months ago (Oct. 9, 2009, 10:24 a.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:59 p.m.)
Indexed	5 days, 17 hours ago (Aug. 28, 2025, 8:36 a.m.)
Issued	15 years, 10 months ago (Oct. 9, 2009)
Published	15 years, 10 months ago (Oct. 9, 2009)
Published Online	15 years, 10 months ago (Oct. 9, 2009)
Published Print	15 years, 10 months ago (Nov. 1, 2009)

Funders 0

None

BibTeX

@article{Lamb_2009, title={Helicobacter pylori CagA activates NF‐κB by targeting TAK1 for TRAF6‐mediated Lys 63 ubiquitination}, volume={10}, ISSN={1469-3178}, url={http://dx.doi.org/10.1038/embor.2009.210}, DOI={10.1038/embor.2009.210}, number={11}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Lamb, Acacia and Yang, Xiao‐Dong and Tsang, Ying‐Hung N and Li, Jiang‐Dong and Higashi, Hideaki and Hatakeyama, Masanori and Peek, Richard M and Blanke, Steven R and Chen, Lin‐Feng}, year={2009}, month=oct, pages={1242–1249} }

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