VCP phosphorylation-dependent interaction partners prevent apoptosis in Helicobacter pylori-infected gastric epithelial cells.

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.
Authors	Cheng-Chou Yu, Jyh-Chin Yang, Yen-Ching Chang, Jiing-Guang Chuang, Chung-Wu Lin, Ming-Shiang Wu, Lu-Ping Chow
Journal	PloS one (PLoS One) Vol. 8 Issue 1 Pg. e55724 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID	23383273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins Cell Cycle Proteins Multiprotein Complexes Ubiquitinated Proteins Proto-Oncogene Proteins c-akt Adenosine Triphosphatases VCP protein, human Valosin Containing Protein Vcp protein, mouse
Topics	Adenosine Triphosphatases (metabolism) Animals Apoptosis Carrier Proteins (metabolism) Cell Cycle Proteins (metabolism) Cell Line, Tumor Cell Survival Epithelial Cells (metabolism, microbiology) Gastric Mucosa (metabolism, microbiology) Helicobacter Infections (metabolism) Helicobacter pylori Humans Male Mice Multiprotein Complexes (metabolism) Phosphorylation Protein Binding Protein Interaction Mapping Protein Interaction Maps Proteolysis Proto-Oncogene Proteins c-akt (metabolism) Signal Transduction Ubiquitinated Proteins (metabolism) Valosin Containing Protein

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