Pathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsLim, Michelle C C
Feige, Michael H
Lavrik, Inna N
MetadataShow full item record
AbstractThe human pathogen Helicobacter pylori infects more than half of the world's population and is a paradigm for persistent yet asymptomatic infection but increases the risk for chronic gastritis and gastric adenocarcinoma. For successful colonization, H. pylori needs to subvert the host cell death response, which serves to confine pathogen infection by killing infected cells and preventing malignant transformation. Infection of gastric epithelial cells by H. pylori provokes direct and fast activation of the proinflammatory and survival factor NF-κB, which regulates target genes, such as CXCL8, BIRC3 and TNFAIP3. However, it is not known how H. pylori exploits NF-κB activation and suppresses the inflammatory response and host apoptotic cell death, in order to avert the innate immune response and avoid cell loss, and thereby enhance colonization to establish long-term infection. Here we assign for the first time that H. pylori and also Campylobacter jejuni-induced ubiquitin-editing enzyme A20 bifunctionally terminates NF-κB activity and negatively regulates apoptotic cell death. Mechanistically, we show that the deubiquitinylase activity of A20 counteracts cullin3-mediated K63-linked ubiquitinylation of procaspase-8, therefore restricting the activity of caspase-8. Interestingly, another inducible NF-κB target gene, the scaffold protein p62, ameliorates the interaction of A20 with procaspase-8. In conclusion, pathogen-induced de novo synthesis of A20 regulates the shut-off of the survival factor NF-κB but, on the other hand, also impedes caspase-8-dependent apoptotic cell death so as to promote the persistence of pathogens.Cell Death and Differentiation advance online publication, 2 June 2017; doi:10.1038/cdd.2017.89.
CitationPathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death. 2017 Cell Death Differ.
AffiliationHelmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
JournalCell death and differentiation
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection.
- Authors: Lim MCC, Maubach G, Birkl-Toeglhofer AM, Haybaeck J, Vieth M, Naumann M
- Issue date: 2022 Jan 28
- A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains.
- Authors: Düwel M, Welteke V, Oeckinghaus A, Baens M, Kloo B, Ferch U, Darnay BG, Ruland J, Marynen P, Krappmann D
- Issue date: 2009 Jun 15
- USP48 and A20 synergistically promote cell survival in Helicobacter pylori infection.
- Authors: Jantaree P, Chaithongyot S, Sokolova O, Naumann M
- Issue date: 2022 Aug 1
- A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes.
- Authors: Feoktistova M, Makarov R, Brenji S, Schneider AT, Hooiveld GJ, Luedde T, Leverkus M, Yazdi AS, Panayotova-Dimitrova D
- Issue date: 2020 Feb 3
- A20, an essential component of the ubiquitin-editing protein complex, is a negative regulator of inflammation in human myometrium and foetal membranes.
- Authors: Lappas M
- Issue date: 2017 Sep 1