title: A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity.
abstract: Williams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activity in a significant proportion of human cancers, was identified in this study as a new binding partner for TFII-I and a negative regulator of TFII-I-mediated transcription. These findings suggest a new p53-independent mechanism by which increased Mdm2 levels found in human tumors could influence cancer cells. In addition to that, we present data indicating that TFII-I is an important cellular regulator of transcription from the immediate-early promoter of human cytomegalovirus, a promoter sequence frequently used in mammalian expression vectors, including vectors for gene therapy. Our observation that Mdm2 over-expression can decrease the ability of TFII-I to activate the CMV promoter might have implications for the efficiency of experimental gene therapy based on CMV promoter-derived vectors in cancers with Mdm2 gene amplification.
authors.affiliation: International Clinical Research Center-Center of Biomolecular and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic.|Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Cetkovská
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Šustová
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Pavlína
authors.initials: P
authors.lastname: Kosztyu
authors.affiliation: International Clinical Research Center-Center of Biomolecular and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic.|Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Stjepan
authors.initials: S
authors.lastname: Uldrijan
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019473:Transcription Factors, TFII / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C104259:GTF2I protein, human; D019473:Transcription Factors, TFII; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D001616:beta-Galactosidase