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

Oncogene
Andela HorvatAlexander I Zaika

Abstract

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-bacteri...Continue Reading

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Citations

Mar 7, 2019·Biomolecules·Rosa FontanaMaria Vivo
Sep 6, 2019·Helicobacter·M Constanza CamargoJose C Machado
Dec 6, 2019·Cellular & Molecular Immunology·Atsushi Takahashi-KanemitsuMasanori Hatakeyama
Apr 7, 2020·The Journal of Clinical Investigation·Manikandan PalrasuAlexander I Zaika
Nov 16, 2018·International Journal of Molecular Sciences·Antonio PisanoGiuseppe Fiume
Aug 8, 2020·Biomolecules·Jinho SeoJaewhan Song
Jun 13, 2020·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Boyan HuangYiqun Deng
Nov 18, 2020·International Journal of Molecular Sciences·Manon BrunetMarlène Dufresne
Feb 20, 2021·Pharmacology & Therapeutics·Sunil SinghJ Sivaraman
Apr 4, 2021·International Journal of Molecular Sciences·Lornella SeeneevassenChristine Varon
Apr 8, 2021·Cellular and Molecular Life Sciences : CMLS·Olga Sokolova, Michael Naumann
May 1, 2021·Cancers·Manikandan PalrasuAlexander I Zaika
Jul 2, 2021·BioMed Research International·Sheng-Yu LuYan Cui

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Methods Mentioned

BETA
ubiquitination
immunoprecipitation
transfection

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