title: Control of antioxidative response by the tumor suppressor protein PML through regulating Nrf2 activity.
abstract: Oxidative stress is a consequence of an imbalance between reactive oxygen species (ROS) production and the ability of the cytoprotective system to detoxify the reactive intermediates. The tumor suppressor promyelocytic leukemia protein (PML) functions as a stress sensor. Loss of PML results in impaired mitochondrial complex II activity, increased ROS, and subsequent activation of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidative pathway. We also demonstrate that sulforaphane (SFN), an antioxidant, regulates Nrf2 activity by controlling abundance and subcellular distribution of PML and that PML is essential for SFN-mediated ROS increase, Nrf2 activation, antiproliferation, antimigration, and antiangiogenesis. Taking the results together, we have uncovered a novel antioxidative mechanism by which PML regulates cellular oxidant homeostasis by controlling complex II integrity and Nrf2 activity and identified PML as an indispensable mediator of SFN activity.
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Shuang
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106Comprehensive Cancer Center of Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106 hxk43@cwru.edu.
authors.forename: Hung-Ying
authors.initials: HY
authors.lastname: Kao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013454:Sulfoxides; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C016766:sulforaphane