Recognition of cisplatin-damaged DNA by p53 protein: critical role of the p53 C-terminal domain
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16300733
DOI
10.1016/j.bbrc.2005.11.038
PII: S0006-291X(05)02536-2
Knihovny.cz E-resources
- MeSH
- Cisplatin pharmacology MeSH
- DNA metabolism MeSH
- Antibodies, Monoclonal immunology MeSH
- Tumor Suppressor Protein p53 chemistry genetics immunology metabolism MeSH
- Oxidation-Reduction MeSH
- DNA Damage drug effects MeSH
- Sequence Deletion genetics MeSH
- Substrate Specificity MeSH
- Protein Structure, Tertiary MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cisplatin MeSH
- DNA MeSH
- Antibodies, Monoclonal MeSH
- Tumor Suppressor Protein p53 MeSH
It was shown previously that the p53 protein can recognize DNA modified with antitumor agent cisplatin (cisPt-DNA). Here, we studied p53 binding to the cisPt-DNA using p53 deletion mutants and via modulation of the p53-DNA binding by changes of the protein redox state. Isolated p53 C-terminal domain (CTD) bound to the cisPt-DNA with a significantly higher affinity than to the unmodified DNA. On the other hand, p53 constructs involving the core domain but lacking the C-terminal DNA binding site (CTDBS) exhibited only small binding preference for the cisPt-DNA. Oxidation of cysteine residues within the CD of posttranslationally unmodified full length p53 did not affect its ability to recognize cisPt-DNA. Blocking of the p53 CTDBS by a monoclonal antibody Bp53-10.1 resulted in abolishment of the isolated CTD binding to the cisPt-DNA. Our results demonstrate a crucial role of the basic region of the p53 CTD (aa 363-382) in the cisPt-DNA recognition.
References provided by Crossref.org
The Rich World of p53 DNA Binding Targets: The Role of DNA Structure
Preferential binding of hot spot mutant p53 proteins to supercoiled DNA in vitro and in cells
