Helicobacter pylori pathogen regulates p14ARF tumor suppressor and autophagy in gastric epithelial cells

Autor: Jinxiong Wei, Alexander Zaika, Andela Horvat, Richard M. Peek, Wael El-Rifai, Jennifer M. Noto, Barbara G. Schneider, Manikandan Palrasu, Elena Zaika, Balamurugan Ramatchandirin
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
medicine.disease_cause
TRIP12/ULF
0302 clinical medicine
Tumor Suppressor Protein p14ARF
education.field_of_study
biology
Stomach
ARF
Up-Regulation
3. Good health
Ubiquitin ligase
medicine.anatomical_structure
030220 oncology & carcinogenesis
Signal Transduction
Virulence Factors
Ubiquitin-Protein Ligases
Population
H. pylori
gastric cancer
Down-Regulation
Article
Helicobacter Infections
03 medical and health sciences
Bacterial Proteins
p14arf
Stomach Neoplasms
Cell Line
Tumor
Autophagy
Genetics
medicine
Gastric mucosa
Humans
CagA
education
Molecular Biology
Antigens
Bacterial
Helicobacter pylori
Epithelial Cells
HCT116 Cells
biology.organism_classification
030104 developmental biology
Gastric Mucosa
biology.protein
Cancer research
Tumor Suppressor Protein p53
Carcinogenesis
Zdroj: Oncogene
Popis: Infection with Helicobacter pylori is one of the strongest risk factors for development of gastric cancer. Although these bacteria infect approximately half of the world's population, only a small fraction of infected individuals develops gastric malignancies. Interactions between host and bacterial virulence factors are complex and interrelated, making it difficult to elucidate specific processes associated with H. pylori-induced tumorigenesis. In this study, we found that H. pylori inhibits p14ARF tumor suppressor by inducing its degradation. This effect was found to be strain-specific. Downregulation of p14ARF induced by H. pylori leads to inhibition of autophagy in a p53-independent manner in infected cells. We identified TRIP12 protein as E3 ubiquitin ligase that is upregulated by H. pylori, inducing ubiquitination and subsequent degradation of p14ARF protein. Using isogenic H. pylori mutants, we found that induction of TRIP12 is mediated by bacterial virulence factor CagA. Increased expression of TRIP12 protein was found in infected gastric epithelial cells in vitro and human gastric mucosa of H. pylori-infected individuals. In conclusion, our data demonstrate a new mechanism of ARF inhibition that may affect host-bacteria interactions and facilitate tumorigenic transformation in the stomach.
Databáze: OpenAIRE
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