Yu C.-C.JYH-CHIN YANGChang Y.-C.Chuang J.-G.CHUNG-WU LINMING-SHIANG WULU-PING CHOW2020-01-222020-01-22201319326203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84873201989&doi=10.1371%2fjournal.pone.0055724&partnerID=40&md5=eeba658d2b093f0fb7f85ee69e20259ahttps://scholars.lib.ntu.edu.tw/handle/123456789/452413Previous 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. ? 2013 Yu et al.[SDGs]SDG3phosphatidylinositol 3 kinase; protein kinase B; valosin containing protein; aggresome; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; carcinogenesis; controlled study; disease association; embryo; epithelium cell; functional proteomics; Helicobacter infection; human; human cell; male; mouse; nonhuman; protein degradation; protein function; protein phosphorylation; protein protein interaction; signal transduction; stomach cancer; stomach epithelium; Adenosine Triphosphatases; Animals; Apoptosis; Carrier Proteins; Cell Cycle Proteins; Cell Line, Tumor; Cell Survival; Epithelial Cells; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Mice; Multiprotein Complexes; Phosphorylation; Protein Binding; Protein Interaction Mapping; Protein Interaction Maps; Proteolysis; Proto-Oncogene Proteins c-akt; Signal Transduction; Ubiquitinated Proteinsjournal article10.1371/journal.pone.00557242-s2.0-84873201989