title: Delayed cell cycle progression from SEPW1 depletion is p53- and p21-dependent in MCF-7 breast cancer cells.
abstract: Selenium (Se) is an essential redox-active trace element with close connections to cancer. Most of Se's biological functions have been attributed to the antioxidant properties of Se-containing proteins. However, the relative contribution of selenoproteins and small Se compounds in cancer protection is still a matter of debate. The tumor suppressor p53 is the most frequently mutated gene in human cancer and is often referred to as the "guardian of the genome". In response to genomic stresses, p53 causes cell cycle arrest to allow time for genomic damage to be repaired before cell division or induces apoptosis to eliminate irreparably damaged cells. Selenoprotein W (SEPW1) is a highly conserved small thioredoxin-like protein required for cell cycle progression. The present work shows that SEPW1 facilitates the G1 to S-phase transition by down-regulating expression of the cyclin-dependent kinase inhibitor p21. SEPW1 controls p21 by modulating levels of the p53 transcription factor, and this is associated with changes in phosphorylation of Ser-33 in p53. More work is needed to identify the mechanism by which SEPW1 regulates phosphorylation of Ser-33 and the kinase or phosphatase enzymes involved.
authors.affiliation: USDA Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis, 430 West Health Science Drive, Davis, CA 95616, USA. wayne.hawkes@ars.usda.gov
authors.forename: Wayne Chris
authors.initials: WC
authors.lastname: Hawkes
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Alkan
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D012643:Selenium / Q000378:metabolism; D051151:Selenoprotein W / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; C495240:SELENOW protein, human; D051151:Selenoprotein W; D016159:Tumor Suppressor Protein p53; D012694:Serine; D012643:Selenium