Helicobacter pylori activates NF-κB by inducing Ubc13-mediated ubiquitination of lysine 158 of TAK1

Acacia Lamb, Jinjing Chen, Steven R. Blanke, Lin Feng Chen

Research output: Contribution to journalArticle

Abstract

The Helicobacter pylori virulence factor CagA targets a variety of host proteins to alter different cellular responses, including the induction of pro-inflammatory cytokines. We have previously shown that CagA-facilitated lysine 63-linked ubiquitination of TAK1 is essential for the H. pylori-induced NF-κB activation and the expression of proinflammatory cytokines. However, the molecular mechanism for TAK1 ubiquitination and activation in H. pylori-mediated NF-κB activation remains elusive. Here, we identify lysine 158 of TAK1 as the key residue undergoing lysine 63-linked ubiquitination in response to H. pylori infection. Mutation of lysine 158 to arginine prevents the ubiquitination of TAK1 and impairs H. pylori-induced TAK1 and NF-κB activation. Moreover, we demonstrate that E2 ubiquitin conjugating enzyme Ubc13 is involved in H. pylori-mediated TAK1 ubiquitination. Suppressing the activity of Ubc13 by a dominant-negative mutant or siRNA abolishes CagA-facilitated and H. pylori-induced TAK1 and NF-κB activation. These findings further underscore the importance of lysine 63-linked ubiquitination of TAK1 in H. pylori-induced NF-κB activation and NF-κB-mediated inflammatory response. J. Cell. Biochem. 114: 2284-2292, 2013. © 2013 Wiley Periodicals, Inc.

Original languageEnglish (US)
Pages (from-to)2284-2292
Number of pages9
JournalJournal of Cellular Biochemistry
Volume114
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • CagA
  • NF-κB
  • TAK1
  • UBIQUITINATION
  • Ubc13

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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