Abstract
Previous studies have demonstrated that valosin-containing protein (VCP) is associated with H. pylori-induced gastric carcinogenesis. By identifying the interactome of VCP overexpressed in AGS cells using a subtractive proteomics approach, we aimed to characterize the cellular responses mediated by VCP and its functional roles in H. pylori-associated gastric cancer. VCP immunoprecipitations followed by proteomic analysis identified 288 putative interacting proteins, 18 VCP-binding proteins belonged to the PI3K/Akt signaling pathway. H. pylori infection increased the interaction between Akt and VCP, Akt-dependent phosphorylation of VCP, levels of ubiquitinated proteins, and aggresome formation in AGS cells. Furthermore, phosphorylated VCP co-localized with the aggresome, bound ubiquitinated proteins, and increased the degradation of cellular regulators to protect H. pylori-infected AGS cells from apoptosis. Our study demonstrates that VCP phosphorylation following H. pylori infection promotes both gastric epithelial cell survival, mediated by the PI3K/Akt pathway, and the degradation of cellular regulators. These findings provide novel insights into the mechanisms of H. pylori infection induced gastric carcinogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / metabolism*
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Animals
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Apoptosis*
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Cell Survival
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Epithelial Cells / metabolism*
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Epithelial Cells / microbiology
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Gastric Mucosa / metabolism*
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Gastric Mucosa / microbiology
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Helicobacter Infections / metabolism*
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Helicobacter pylori*
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Humans
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Male
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Mice
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Multiprotein Complexes / metabolism
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Phosphorylation
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Protein Binding
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Protein Interaction Mapping
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Protein Interaction Maps
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Proteolysis
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction
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Ubiquitinated Proteins / metabolism
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Valosin Containing Protein
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Multiprotein Complexes
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Ubiquitinated Proteins
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Proto-Oncogene Proteins c-akt
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Adenosine Triphosphatases
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VCP protein, human
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Valosin Containing Protein
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Vcp protein, mouse
Grants and funding
This work was supported in part by the Program for Excellence Research Teams of the Ministry of Education, Grant 98-2320-B-002-030-MY3 from the National Science Council, and Liver Disease Prevention & Treatment Research Foundation, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.