title: Reactive oxygen species-dependent down-regulation of tumor suppressor genes PTEN, USP28, DRAM, TIGAR, and CYLD under oxidative stress.
abstract: We examined whether steady-state mRNA levels of five tumor suppressor genes are subjected to oxidative stress. Superoxide radical-generating menadione and serum deprivation diminished the steady-state mRNA levels for the genes phosphatase and tensin homolog (PTEN), ubiquitin specific peptidase 28 (USP28), damage-regulated autophagy modulator (DRAM), TP53-induced glycolysis and apoptosis regulator (TIGAR), and cylindromatosis (CYLD). Hydrogen peroxide showed suppression in steady-state mRNA levels for USP28, DRAM, TIGAR, and CYLD but not for PTEN. The steady-state mRNA levels specific for all five genes were enhanced by antioxidants, such as glutathione and N-acetylcysteine. The HepG2 stable transfectants overexpressing the mitochondrial isoform of human glutaredoxin, Grx2a, and containing a relatively low reactive oxygen species (ROS) level were assessed to contain the increased steady-state mRNA levels specific for the five tumor suppressor genes. In brief, the steady-state mRNA levels specific for these genes are negatively regulated by oxidative stress through the mediation of ROS.
authors.affiliation: Department of Biochemistry, Kangwon National University, Hyoja-2-dong, 192-1, Chuncheon, 200-701, Korea.
authors.forename: Su-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Jung
authors.forename: Chang-Jin
authors.initials: CJ
authors.lastname: Lim
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D000074749:Deubiquitinating Enzyme CYLD; D015536:Down-Regulation; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D054477:Glutaredoxins / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C512709:DRAM1 protein, human; D054477:Glutaredoxins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C442902:USP28 protein, human; D013481:Superoxides; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D043222:Ubiquitin Thiolesterase