Journal article
Helicobacter pylori affects the cellular deubiquitinase USP7 and ubiquitin-regulated components TRAF6 and the tumour suppressor p53
International journal of medical microbiology, Vol.301(3), pp.213-224
03/01/2011
DOI: 10.1016/j.ijmm.2010.09.004
PMID: 21131231
Abstract
Helicobacter pylori is a recognized cancerogenic bacterial agent in humans, associated with gastritis, peptic ulcer, and gastric cancer. Immunoevasive and immunomodulatory mechanisms underlie the chronic persistence of the bacterium and the active proinflammatory effect of life-long
H. pylori infection. In contrast to tumorigenic viruses, which frequently possess factors to influence the host ubiquitin-proteasome system (UPS), nothing is yet known about potential effects of
H. pylori in this respect. The majority of
H. pylori isolates worldwide possess a pathogenicity island (PAI), the
cagPAI, which is involved in IL-8 production and chronic inflammation. We hypothesized that
H. pylori and its
cagPAI may have an influence on host cell ubiquitin pathways.
The effect of
H. pylori wild type and isogenic mutants lacking the complete
cagPAI (or CagA) on host deubiqutinating enzymes (DUBs) was tested in coincubation experiments with human gastric epithelial cells, using DUB activity profiling. Specific DUBs were identified to be active in gastric cells. Effects on the activity and expression of DUBs were observed in
H. pylori-infected cells. In particular,
H. pylori caused a strong decrease in the expression and activity of the DUB USP7 which was partially
cagPAI- and CagA-dependent. The reduction in USP7 in infected cells at the protein and transcript levels coincided with a decrease in the amounts of the major innate immune hub protein TRAF6 and the tumor suppressor p53. These results are a basis for further investigations into
H. pylori modulators of ubiquitin-dependent cellular signaling and their biological function.
Details
- Title: Subtitle
- Helicobacter pylori affects the cellular deubiquitinase USP7 and ubiquitin-regulated components TRAF6 and the tumour suppressor p53
- Creators
- Nina Coombs - Medizinische Hochschule HannoverRamakrishna Sompallae - Karolinska InstitutetPatrick Olbermann - Medizinische Hochschule HannoverStefano Gastaldello - Karolinska InstitutetDaniela Göppel - Medizinische Hochschule HannoverMaria G. Masucci - Karolinska InstitutetChristine Josenhans - Medizinische Hochschule Hannover
- Resource Type
- Journal article
- Publication Details
- International journal of medical microbiology, Vol.301(3), pp.213-224
- Publisher
- Elsevier GmbH
- DOI
- 10.1016/j.ijmm.2010.09.004
- PMID
- 21131231
- ISSN
- 1438-4221
- eISSN
- 1618-0607
- Language
- English
- Date published
- 03/01/2011
- Academic Unit
- Pathology
- Record Identifier
- 9984622757902771
Metrics
5 Record Views