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Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation.


Chronic infection with cagA-positive Helicobacter pylori is the strongest risk factor for the development of gastric adenocarcinoma. The cagA gene product CagA is injected into gastric epithelial cells and disturbs cellular functions by physically interacting with and deregulating a variety of cellular signaling molecules. RUNX3 is a tumor suppressor in many tissues, and it is frequently inactivated in gastric cancer. In this study, we show that H. pylori infection inactivates the gastric tumor suppressor RUNX3 in a CagA-dependent manner. CagA directly associates with RUNX3 through a specific recognition of the PY motif of RUNX3 by a WW domain of CagA. Deletion of the WW domains of CagA or mutation of the PY motif in RUNX3 abolishes the ability of CagA to induce the ubiquitination and degradation of RUNX3, thereby extinguishing its ability to inhibit the transcriptional activation of RUNX3. Our studies identify RUNX3 as a novel cellular target of H. pylori CagA and also reveal a mechanism by which CagA functions as an oncoprotein by blocking the activity of gastric tumor suppressor RUNX3.

Pubmed ID: 20676134


  • Tsang YH
  • Lamb A
  • Romero-Gallo J
  • Huang B
  • Ito K
  • Peek RM
  • Ito Y
  • Chen LF



Publication Data

October 14, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-116087
  • Agency: NCI NIH HHS, Id: CA-77955
  • Agency: NIDDK NIH HHS, Id: DK-085158
  • Agency: NIDDK NIH HHS, Id: DK-58587
  • Agency: NIDDK NIH HHS, Id: P30 DK058404-10
  • Agency: NCI NIH HHS, Id: R01 CA077955
  • Agency: NCI NIH HHS, Id: R01 CA077955-06
  • Agency: NIDDK NIH HHS, Id: R01 DK058587
  • Agency: NIDDK NIH HHS, Id: R01 DK058587-01A1
  • Agency: NIDDK NIH HHS, Id: R01 DK085158
  • Agency: NIDDK NIH HHS, Id: R01 DK085158-02

Mesh Terms

  • Amino Acid Motifs
  • Animals
  • Antigens, Bacterial
  • Bacterial Proteins
  • Binding Sites
  • COS Cells
  • Cell Line
  • Cell Line, Tumor
  • Cercopithecus aethiops
  • Core Binding Factor Alpha 3 Subunit
  • Gastric Mucosa
  • Helicobacter Infections
  • Helicobacter pylori
  • Host-Pathogen Interactions
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Immunoprecipitation
  • Mice
  • Mutation
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Stomach Neoplasms
  • Transfection