TY - JOUR
T1 - Regulation of expression of the p21CIP1 gene by the transcription factor ZNF217 and MDM2
AU - Mantsou, Aglaia
AU - Koutsogiannouli, Evangelia
AU - Haitoglou, Costas
AU - Papavassiliou, Athanasios G.
AU - Papanikolaou, Nikolaos A.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Affinity chromatography
KW - MDM2
KW - P21 promoter
KW - ZNF217
UR - http://www.scopus.com/inward/record.url?scp=84995791220&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995791220&partnerID=8YFLogxK
U2 - 10.1139/bcb-2016-0026
DO - 10.1139/bcb-2016-0026
M3 - Article
AN - SCOPUS:84995791220
SN - 0829-8211
VL - 94
SP - 560
EP - 568
JO - Biochemistry and Cell Biology
JF - Biochemistry and Cell Biology
IS - 6
ER -