title: Regulation of expression of the p21CIP1gene by the transcription factor ZNF217 and MDM2.
abstract: Using mouse double minute 2 (MDM2) protein-specific affinity chromatography and mass spectrometry, we have isolated the protein product of the oncogene znf217, which is a transcription factor and a component of a Hela-S-derived HDAC1 complex, as a novel MDM2-interacting protein. When co-expressed in cultured cancer cells, ZNF217 forms a complex with MDM2 and its ectopic over-expression reduces the steady-state levels of acetylated p53 in cell lines, suppressing its ability to activate the expression of a p21 promoter construct. In-silico analysis of the p21 promoter revealed the presence of several ZNF217-binding sites. These findings suggest that MDM2 controls p21 expression by at least 2 mechanisms: through ZNF217-mediated recruitment of HDAC1/MDM2 activity, which inhibits p53 acetylation; and through direct interaction with its binding site(s) on the p21 promoter.
authors: a Laboratory of Biological Chemistry, Division of Biological Sciences and Preventive Medicine, Faculty of Medicine, Aristotle University of Thessaloniki, University Campus Bldg 16a, 54124 Thessaloniki, Greece.
authors: Aglaia
authors: A
authors: Mantsou
authors: a Laboratory of Biological Chemistry, Division of Biological Sciences and Preventive Medicine, Faculty of Medicine, Aristotle University of Thessaloniki, University Campus Bldg 16a, 54124 Thessaloniki, Greece.
authors: Evangelia
authors: E
authors: Koutsogiannouli
authors: a Laboratory of Biological Chemistry, Division of Biological Sciences and Preventive Medicine, Faculty of Medicine, Aristotle University of Thessaloniki, University Campus Bldg 16a, 54124 Thessaloniki, Greece.
authors: Costas
authors: C
authors: Haitoglou
authors: b Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street, 11527 Athens, Greece.
authors: Athanasios G
authors: AG
authors: Papavassiliou
authors: a Laboratory of Biological Chemistry, Division of Biological Sciences and Preventive Medicine, Faculty of Medicine, Aristotle University of Thessaloniki, University Campus Bldg 16a, 54124 Thessaloniki, Greece.
authors: Nikolaos A
authors: NA
authors: Papanikolaou
mesh_terms: D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C113698:ZNF217 protein, human; D008156:Luciferases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Affinity chromatography; MDM2; ZNF217; chromatographie d’affinité; p21 promoter; promoteur de p21