title: 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 Δ133p53 and Δ160p53 isoforms in human cells. Induction of an orthologous p53 isoform, Δ153p53, was also found in H. pylori-infected Mongolian gerbils. The p53 isoforms inhibit p53 and p73 activities, induce NF-κB, and increase survival of infected cells. Expression of Δ133p53, 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.
authors.affiliation: Department of Surgery, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
authors.forename: Jinxiong
authors.initials: J
authors.lastname: Wei
authors.forename: Jennifer
authors.initials: J
authors.lastname: Noto
authors.forename: Elena
authors.initials: E
authors.lastname: Zaika
authors.forename: Judith
authors.initials: J
authors.lastname: Romero-Gallo
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.forename: Wael
authors.initials: W
authors.lastname: El-Rifai
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Alexander
authors.initials: A
authors.lastname: Zaika
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005849:Gerbillinae; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D020033:Protein Isoforms; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D020033:Protein Isoforms; C495901:TP53 protein, human; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53