title: A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation.
abstract: The pentose phosphate pathway (PPP) provides ribose and NADPH that support biosynthesis and antioxidant defense. Our recent findings suggest that the p53-related protein TAp73 enhances the PPP flux. TAp73 stimulates the expression of glucose-6-phophate dehydrogenase (G6PD), the rate-limiting enzymes of the PPP. Through this regulation, TAp73 promotes the accumulation of macromolecules and increases cellular capability to withstand oxidative stresses. TAp73 also regulates other metabolic enzymes, and the relative importance of these targets in TAp73-mediated cell growth is not well understood. Here we show that, like in other cell lines, TAp73 is required for supporting proliferation and maintaining the expression of G6PD in the human lung cancer H1299 cells. Restoration of G6PD expression almost fully rescues the defects in cell growth caused by TAp73 knockdown, suggesting that G6PD is the major proliferative target of TAp73 in these cells. G6PD expression is elevated in various tumors, correlating with the upregulation of TAp73. These results indicate that TAp73 may function as an oncogene, and that G6PD is likely a focal point of regulation in oncogenic growth.
authors.affiliation: Department of Cancer Biology and Abramson Family Cancer Research Institute; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Cancer Biology and Abramson Family Cancer Research Institute; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Cancer Biology and Abramson Family Cancer Research Institute; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D005954:Glucosephosphate Dehydrogenase
keywords: G6PD; ROS; TAp73; cell proliferation; metabolism; p73; pentose phosphate pathway