Pathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death.

5.00
Hdl Handle:
http://hdl.handle.net/10033/620980
Title:
Pathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death.
Authors:
Lim, Michelle C C; Maubach, Gunter; Sokolova, Olga; Feige, Michael H; Diezko, Rolf; Buchbinder, Jörn; Backert, Steffen; Schlüter, Dirk; Lavrik, Inna N; Naumann, Michael
Abstract:
The 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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
Citation:
Pathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death. 2017 Cell Death Differ.
Journal:
Cell death and differentiation
Issue Date:
2-Jun-2017
URI:
http://hdl.handle.net/10033/620980
DOI:
10.1038/cdd.2017.89
PubMed ID:
28574503
Type:
Article
Language:
en
ISSN:
1476-5403
Appears in Collections:
publications of the scientific administration (GFW)

Full metadata record

DC FieldValue Language
dc.contributor.authorLim, Michelle C Cen
dc.contributor.authorMaubach, Gunteren
dc.contributor.authorSokolova, Olgaen
dc.contributor.authorFeige, Michael Hen
dc.contributor.authorDiezko, Rolfen
dc.contributor.authorBuchbinder, Jörnen
dc.contributor.authorBackert, Steffenen
dc.contributor.authorSchlüter, Dirken
dc.contributor.authorLavrik, Inna Nen
dc.contributor.authorNaumann, Michaelen
dc.date.accessioned2017-06-26T13:27:52Z-
dc.date.available2017-06-26T13:27:52Z-
dc.date.issued2017-06-02-
dc.identifier.citationPathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death. 2017 Cell Death Differ.en
dc.identifier.issn1476-5403-
dc.identifier.pmid28574503-
dc.identifier.doi10.1038/cdd.2017.89-
dc.identifier.urihttp://hdl.handle.net/10033/620980-
dc.description.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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titlePathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.en
dc.identifier.journalCell death and differentiationen

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