Helicobacter pylori activates NF‐κB by inducing Ubc13‐mediated ubiquitination of lysine 158 of TAK1. Issue 10 (16th August 2013)

• Record Type: Journal Article
• Authors: Lamb, Acacia; Chen, JinJing; Blanke, Steven R.; Chen, Lin‐Feng
• Is Part Of: Journal of cellular biochemistry. Volume 114:Issue 10(2013:Oct.)
• Page Start: 2284
• Page End: 2292
• Publication Date: 2013-08-16
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.24573
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jcb24573-sec-0001" sec-type="section"> <p>The <italic>Helicobacter pylori</italic> 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 <italic>H. pylori</italic>‐induced NF‐κB activation and the expression of proinflammatory cytokines. However, the molecular mechanism for TAK1 ubiquitination and activation in <italic>H. pylori</italic>‐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 <italic>H. pylori</italic> infection. Mutation of lysine 158 to arginine prevents the ubiquitination of TAK1 and impairs <italic>H. pylori</italic>‐induced TAK1 and NF‐κB activation. Moreover, we demonstrate that E2 ubiquitin conjugating enzyme Ubc13 is involved in <italic>H. pylori</italic>‐mediated TAK1 ubiquitination. Suppressing the activity of Ubc13 by a dominant‐negative mutant or siRNA abolishes CagA‐facilitated and <italic>H. pylori</italic>‐induced TAK1 and NF‐κB activation. These findings further underscore the importance of lysine 63‐linked ubiquitination of TAK1 in <italic>H. pylori</italic>‐induced NF‐κB activation and NF‐κB‐mediated inflammatory response. J. Cell. Biochem. 114: 2284–2292, 2013. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>