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PMID: 8334996 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sequence-specific DNA binding by p53: identification of target sites and lack of binding to p53 - MDM2 complexes.

The EMBO journal ·Vol. 12 ·No. 7 ·1993-07-00 ·Pages 2799-808

Zauberman A, Barak Y, Ragimov N, Levy N, Oren M

Abstract

An immune selection procedure was employed in order to isolate p53 binding sites from mouse genomic DNA. Two DNA clones capable of tight specific interaction with wild type p53 were subjected to further characterization. In both cases, the p53 binding regions displayed a high degree of sequence homology with the consensus binding site defined for human genomic DNA. One of the clones was found to be derived from the LTR of a retrovirus-like element (a member of the GLN family). The region encompassing the GLN LTR p53 binding site could confer p53 responsiveness upon a heterologous promoter. Furthermore, the expression of the endogenous, chromosomally integrated GLN elements was significantly induced upon activation of wild type p53 in cells harboring a temperature sensitive p53 mutant. Finally, it was demonstrated that p53 - MDM2 complexes fail to bind tightly to such a p53 binding site. This may contribute to the inhibition by MDM2 of p53-mediated transcriptional activation.

MeSH Terms
Animals Base Sequence Binding Sites Cell Line DNA/metabolism Humans Mice Mice, Inbred C57BL Molecular Sequence Data Neoplasm Proteins/metabolism Nuclear Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-mdm2 Rats Transcriptional Activation Tumor Suppressor Protein p53/metabolism
Chemicals
Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins Tumor Suppressor Protein p53 DNA MDM2 protein, human Mdm2 protein, mouse Mdm2 protein, rat Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zauberman A
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Barak Y
Ragimov N
Levy N
Oren M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-07-00
Pages
2799-808
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413530
Subset
IM
Grants
NCI NIH HHS · R01 CA40099 · United States
Databases
GENBANK
X72083, X72084
External Links
PubMed source PMC Full Text View journal details
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