title: NQO1 Stabilizes p53 in Response to Oncogene-Induced Senescence.
abstract: Cellular senescence is a state of permanent cellular arrest that provides an initial barrier to cell transformation and tumorigenesis. In this study, we report that expression of
  quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, is induced during oncogene-induced senescence (OIS). Depletion of NQO1 resulted in the delayed onset of senescence. In contrast, ectopic expression of NQO1 enhanced the senescence phenotype. Analysis of the mechanism underlying the up-regulation of NQO1 expression during senescence identified that NQO1 promotes p53 accumulation in an MDM2 and ubiquitin independent manner, which reinforces the cellular senescence phenotype. Specifically, we demonstrated that NRF2/KEAP1 signaling regulates NQO1 expression during OIS. More importantly, we confirmed that depletion of NQO1 facilitates cell transformation and tumorigenesis, which indicates that NQO1 takes part in the senescence barrier and has anti-oncogenic properties in cell transformation.
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Liu
authors.affiliation: 2. Department of Clinical Laboratory, Peking University First Hospital, Beijing, 100034 People's Republic of China;
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.affiliation: 3. Center of Basic Medical Sciences, Navy General Hospital; Beijing, 100048 People's Republic of China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Wu
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Jianming
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Xiangwen
authors.initials: X
authors.lastname: Zhan
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Shen
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center; Beijing, 100191 People's Republic of China;
authors.forename: Zebin
authors.initials: Z
authors.lastname: Mao
mesh_terms: D001973:Bromodeoxyuridine; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008156:Luciferases; D016297:Mutagenesis, Site-Directed; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001616:beta-Galactosidase
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine
keywords: NQO1; p53; senescence