Regulation of expression of the p21 gene by the transcription factor ZNF217 and MDM2.
Τίτλος | Regulation of expression of the p21 gene by the transcription factor ZNF217 and MDM2. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Mantsou, A., Koutsogiannouli E., Haitoglou C., Papavassiliou A. G., & Papanikolaou N. A. |
Journal | Biochem Cell Biol |
Volume | 94 |
Issue | 6 |
Pagination | 560-568 |
Date Published | 2016 Dec |
ISSN | 1208-6002 |
Λέξεις κλειδιά | Acetylation, Animals, Base Sequence, Carcinoma, Non-Small-Cell Lung, Cyclin-Dependent Kinase Inhibitor p21, Gene Expression Regulation, Neoplastic, Humans, Luciferases, Lung Neoplasms, Mice, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-mdm2, Trans-Activators, Tumor Cells, Cultured, Tumor Suppressor Protein p53 |
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. |
DOI | 10.1139/bcb-2016-0026 |
Alternate Journal | Biochem. Cell Biol. |
PubMed ID | 27792410 |