RRC ID 12386
Author Coombs N, Sompallae R, Olbermann P, Gastaldello S, Göppel D, Masucci MG, Josenhans C.
Title Helicobacter pylori affects the cellular deubiquitinase USP7 and ubiquitin-regulated components TRAF6 and the tumour suppressor p53.
Journal Int. J. Med. Microbiol.
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.
Volume 301(3)
Pages 213-24
Published 2011-3
DOI 10.1016/j.ijmm.2010.09.004
PII S1438-4221(10)00107-4
PMID 21131231
MeSH Cells, Cultured Coculture Techniques Down-Regulation Epithelial Cells / microbiology Gene Expression Gene Expression Profiling Genomic Islands Helicobacter pylori / metabolism* Helicobacter pylori / pathogenicity* Host-Pathogen Interactions* Humans Sequence Deletion TNF Receptor-Associated Factor 6 / biosynthesis* Tumor Suppressor Protein p53 / biosynthesis* Ubiquitin Thiolesterase / biosynthesis* Ubiquitin-Specific Peptidase 7 Virulence Factors / genetics
IF 3.362
Times Cited 5
Human and Animal Cells MKN45 (RCB1001)