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Oncogene. 1997 Mar 20;14(11):1371-6.

Specific p53-DNA complexes contain an mdm2-related protein.

Author information

1
YCRC P53 Research Group, Department of Biology, University of York, UK.

Abstract

The mdm2 gene encodes a family of proteins, a subset of which bind p53 and negatively regulate its function as a transcription factor. We now show that an anti-mdm-2 monoclonal antibody, 2A10, recognises a protein present in rabbit reticulocyte lysate which binds murine p53 translated in vitro. Deletion of p53 residues 10-35, which encompass the mdm-2 binding site, abolished binding of this 2A10-reactive protein. Binding was also dependent upon p53 protein conformation and may require nascent p53 polypeptide since binding was lost following conformational shifting of the temperature-sensitive mutant A135V. Previous studies have shown that mdm-2-p53 complexes fail to exhibit detectable sequence-specific DNA binding. However, our present results demonstrate that p53 in complex with an mdm-2-related protein in vitro retained sequence-specific DNA binding capacity. Non-transformed (but not transformed) 3T3 cells were also found to express a similar 2A10-reactive protein, detectable by gel shift analysis of cellular p53 in complex with a specific DNA target. Mdm-2 in rabbit reticulocyte lysate and in normal, non-transformed 3T3 cells may represent constitutively expressed protein. Our results raise the possibility that constitutive mdm-2 may enhance and/or suppress functions of p53 as yet unidentified.

PMID:
9178897
DOI:
10.1038/sj.onc.1200962
[Indexed for MEDLINE]
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