1. Regulation of expression of the p21CIP1 gene by the transcription factor ZNF217 and MDM2
- Author
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Mantsou, A. Koutsogiannouli, E. Haitoglou, C. Papavassiliou, A.G. Papanikolaou, N.A.
- Subjects
enzymes and coenzymes (carbohydrates) - 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. © 2016 Published by NRC Research Press.
- Published
- 2016