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Regulation of expression of the p21 gene by the transcription factor ZNF217 and MDM2.

ΤίτλοςRegulation of expression of the p21 gene by the transcription factor ZNF217 and MDM2.
Publication TypeJournal Article
Year of Publication2016
AuthorsMantsou, A., Koutsogiannouli E., Haitoglou C., Papavassiliou A. G., & Papanikolaou N. A.
JournalBiochem Cell Biol
Volume94
Issue6
Pagination560-568
Date Published2016 Dec
ISSN1208-6002
Λέξεις κλειδιάAcetylation, 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.

DOI10.1139/bcb-2016-0026
Alternate JournalBiochem. Cell Biol.
PubMed ID27792410

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