title: Hydrogen peroxide controls Akt activity via ubiquitination/degradation             pathways.
abstract: Akt is a well-established protein that regulates cell growth, survival and             anti-apoptotic mechanisms. In this study, we demonstrated that hydrogen peroxide             (H2O2)-induced oxidative stress regulates the activity of the anti-apoptotic protein             Akt via the ubiquitin-proteasome degradation system. H2O2 induced cytotoxicity             in PC12 cells and decreased the cellular protein and phosphorylation levels of             Akt in a concentration- and exposure time-dependent manner. This downregulation             was blocked by the proteasome inhibitor MG132 and the Akt-specific inhibitor LY294002.             In addition, an in vivo ubiquitination assay revealed that the degradation of             Akt was mediated by the ubiquitin-mediated proteasome pathway and further demonstrated             that this ubiquitination was dependent on the phosphorylation status of Akt. Furthermore,             the exogenously overexpressed active form of Akt, but not its inactive form, induced             resistance to H2O2-mediated cell death. These results suggested that H2O2-induced             cytotoxicity was mediated by active Akt degradation.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University                     School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746,                     Republic of Korea.
authors.forename: Sun-Yong
authors.initials: SY
authors.lastname: Kim
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
authors.forename: Keun-Hee
authors.initials: KH
authors.lastname: Choi
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D016716:PC12 Cells; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D054875:Ubiquitination / Q000187:drug effects*
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex