title: Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect.
abstract: Regulation of energy metabolism is a novel function of p53 in tumor suppression. Parkin (PARK2), a Parkinson disease-associated gene, is a potential tumor suppressor whose expression is frequently diminished in tumors. Here Parkin was identified as a p53 target gene that is an important mediator of p53's function in regulating energy metabolism. The human and mouse Parkin genes contain functional p53 responsive elements, and p53 increases the transcription of Parkin in both humans and mice. Parkin contributes to the function of p53 in glucose metabolism; Parkin deficiency activates glycolysis and reduces mitochondrial respiration, leading to the Warburg effect. Restoration of Parkin expression reverses the Warburg effect in cells. Thus, Parkin deficiency is a novel mechanism for the Warburg effect in tumors. Parkin also contributes to the function of p53 in antioxidant defense. Furthermore, Parkin deficiency sensitizes mice to γ-irradiation-induced tumorigenesis, which provides further direct evidence to support a role of Parkin in tumor suppression. Our results suggest that as a novel component in the p53 pathway, Parkin contributes to the functions of p53 in regulating energy metabolism, especially the Warburg effect, and antioxidant defense, and thus the function of p53 in tumor suppression.
authors.affiliation: Department of Radiation Oncology and Department of Pediatrics, Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Cen
authors.initials: C
authors.lastname: Zhang
authors.forename: Meihua
authors.initials: M
authors.lastname: Lin
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Wenwei
authors.initials: W
authors.lastname: Hu
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D016147:Genes, Tumor Suppressor; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D005947:Glucose