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

Area of Science:

• Molecular Biology
• Oncology
• Microbiology

Background:

• The p53 protein is a crucial tumor suppressor, halting cell proliferation and inducing apoptosis or cell cycle arrest in response to cellular stress.
• Emerging evidence highlights the importance of p53 isoform-specific functions in cellular processes.
• Helicobacter pylori is strongly associated with gastric cancer and MALT lymphoma.

Purpose of the Study:

• To investigate the impact of Helicobacter pylori infection on p53 protein expression and its isoforms.
• To elucidate the role of specific p53 isoforms in H. pylori-associated tumorigenesis.

Main Methods:

• Analysis of p53 isoform expression in human gastric epithelial cells infected with H. pylori.
• Investigation of H. pylori-mediated induction of p53 isoforms (Δ133p53, Δ160p53) via the cag pathogenicity island.
• Assessment of p53 isoform activity, including inhibition of p53 and p73, induction of NF-κB, and cell survival.
• Examination of the regulatory mechanisms of Δ133p53 expression, involving c-Jun phosphorylation and AP-1-dependent transcription.

Main Results:

• H. pylori infection induces N-terminally truncated p53 isoforms, Δ133p53 and Δ160p53, in gastric epithelial cells.
• An orthologous p53 isoform, Δ153p53, was induced in H. pylori-infected gerbils.
• These p53 isoforms inhibit p53 and p73 activities, activate NF-κB signaling, and enhance the survival of infected cells.
• Δ133p53 expression is regulated by c-Jun phosphorylation and AP-1 transcriptional activity.

Conclusions:

• H. pylori infection can alter the p53 expression profile towards inhibitory isoforms.
• Induced p53 isoforms may contribute to gastric tumorigenesis by promoting cell survival and modulating key signaling pathways.
• These findings offer insights into the molecular mechanisms underlying H. pylori-associated gastric diseases.