Regulation of expression of the p21CIP1 gene by the transcription factor ZNF217 and MDM2

Aglaia Mantsou, Evangelia Koutsogiannouli, Costas Haitoglou, Athanasios G. Papavassiliou, Nikolaos A. Papanikolaou

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)560-568
Number of pages9
JournalBiochemistry and Cell Biology
Volume94
Issue number6
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • Affinity chromatography
  • MDM2
  • P21 promoter
  • ZNF217

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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