title: p53 as a retrovirus-induced oxidative stress modulator.
abstract: Infection of astrocytes by the neuropathogenic mutant of Moloney murine leukemia virus, ts1, exhibits increased levels of reactive oxygen species (ROS) and signs of oxidative stress compared with uninfected astrocytes. Previously, we have demonstrated that ts1 infection caused two separate events of ROS upregulation. The first upregulation occurs during early viral establishment in host cells and the second during the virus-mediated apoptotic process. In this study, we show that virus-mediated ROS upregulation activates the protein kinase, ataxia telangiectasia mutated, which in turn phosphorylates serine 15 on p53. This activation of p53 however, is unlikely associated with ts1-induced cell death. Rather p53 appears to be involved in suppressing intracellular ROS levels in astrocytes under oxidative stress. The activated p53 appears to delay retroviral gene expression by suppressing NADPH oxidase, a superoxide-producing enzyme. These results suggest that p53 plays a role as a retrovirus-mediated oxidative stress modulator.
authors.affiliation: Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Smithville, TX, USA.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Smithville, TX, USA.
authors.forename: Paul K Y
authors.initials: PKY
authors.lastname: Wong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000821:virology; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000821:virology; D001921:Brain / Q000378:metabolism / Q000821:virology; D016923:Cell Death / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D019255:NADPH Oxidases