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Helicobacter pylori activates NF‐κB by inducing Ubc13‐mediated ubiquitination of lysine 158 of TAK1
Author(s) -
Lamb Acacia,
Chen JinJing,
Blanke Steven R.,
Chen LinFeng
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24573
Subject(s) - lysine , helicobacter pylori , ubiquitin , nf κb , chemistry , microbiology and biotechnology , biochemistry , biology , signal transduction , amino acid , genetics , gene
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.