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Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses.

ABSTRACT: The p53 protein plays a central role in the prevention of tumorigenesis. Cellular stresses, such as DNA damage and aberrant oncogene activation, trigger induction of p53 that halts cellular proliferation and allows cells to be repaired. If cellular damage is beyond the capability of the repair mechanisms, p53 induces apoptosis or cell cycle arrest, preventing damaged cells from becoming cancerous. However, emerging evidence suggests that the function of p53 needs to be considered as isoform-specific. Here, we report that the expression profile of p53 can be shifted toward inhibitory p53 isoforms by the pathogenic bacterium Helicobacter pylori, which is known for its strong association with gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. We found that interaction of H. pylori with gastric epithelial cells, mediated via the cag pathogenicity island, induces N-terminally truncated ?133p53 and ?160p53 isoforms in human cells. Induction of an orthologous p53 isoform, ?153p53, was also found in H. pylori-infected Mongolian gerbils. The p53 isoforms inhibit p53 and p73 activities, induce NF-?B, and increase survival of infected cells. Expression of ?133p53, in response to H. pylori infection, is regulated by phosphorylation of c-Jun and activation of activator protein-1-dependent transcription. Together, these results provide unique insights into the regulation of p53 protein and may contribute to the understanding of tumorigenesis associated with H. pylori.

SUBMITTER: Wei J

PROVIDER: S-EPMC3458371 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses.

Wei Jinxiong J Noto Jennifer J Zaika Elena E Romero-Gallo Judith J Correa Pelayo P El-Rifai Wael W Peek Richard M RM Zaika Alexander A

Proceedings of the National Academy of Sciences of the United States of America 20120827 38

The p53 protein plays a central role in the prevention of tumorigenesis. Cellular stresses, such as DNA damage and aberrant oncogene activation, trigger induction of p53 that halts cellular proliferation and allows cells to be repaired. If cellular damage is beyond the capability of the repair mechanisms, p53 induces apoptosis or cell cycle arrest, preventing damaged cells from becoming cancerous. However, emerging evidence suggests that the function of p53 needs to be considered as isoform-spec ...[more]

PMID: 22927405

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Project description:ObjectiveInfection with Helicobacter pylori (H pylori), especially cytotoxin-associated gene A-positive (CagA+) strains, has been associated with various gastrointestinal and extragastric diseases. The aim of this study was to characterize H pylori-induced alterations in the gastric and tongue coating microbiota and evaluate their potential impacts on human health.DesignThe gastric mucosa and tongue coating specimens were collected from 80 patients with chronic gastritis, and microbiota profiles were generated by 16S rRNA gene sequencing. Samples were grouped as H pylori negative (n = 32), CagA-negative H pylori infection (n = 13), and CagA-positive H pylori infection (n=35). The comparison of bacterial relative abundance was made using a generalized linear model. Functional profiling of microbial communities was predicted with PICRUSt and BugBase. Microbial correlation networks were produced by utilizing SparCC method.ResultsSignificant alterations of the gastric microbiota were found in the H pylori+/CagA+ samples, represented by a decrease in bacterial diversity, a reduced abundance of Roseburia, and increased abundances of Helicobacter and Haemophilus genera. At the community level, functions involved in biofilm forming, mobile element content, and facultative anaerobiosis were significantly decreased in gastric microbiome of the H pylori+ subjects. The presence of CagA gene was linked to an increased proportion of Gram-negative bacteria in the stomach, thereby contributing to an upregulation of lipopolysaccharide (LPS) biosynthesis. The number of bacterial interactions was greatly reduced in networks of both tongue coating and gastric microbiota of the H pylori+/CagA+ subject, and the cooperative bacterial interactions dominated the tongue coating microbiome.ConclusionsInfection with H pylori strains possessing CagA may increase the risk of various diseases, by upregulating LPS biosynthesis in the stomach and weakening the defense of oral microbiota against microorganisms with pathogenic potential.

Dataset Information

Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses.

Publications

Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses.

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