A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity
| Autor: | Stjepan Uldrijan, Pavlína Kosztyu, Hana Šustová, Kateřina Cetkovská |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Transcription
Genetic Response element Regulator Cytomegalovirus lcsh:Medicine Biology Transcription Factors TFII 03 medical and health sciences 0302 clinical medicine Genes Reporter Cell Line Tumor Gene expression Transcriptional regulation Humans Luciferases Promoter Regions Genetic lcsh:Science Transcription factor Cell Proliferation 030304 developmental biology Regulation of gene expression 0303 health sciences Binding Sites Multidisciplinary HEK 293 cells lcsh:R Proto-Oncogene Proteins c-mdm2 beta-Galactosidase Molecular biology 3. Good health Cell biology Gene Expression Regulation Neoplastic HEK293 Cells 030220 oncology & carcinogenesis biology.protein Mdm2 lcsh:Q Tumor Suppressor Protein p53 Protein Binding Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 12, p e0144753 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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