Interaction of C-terminal p53 isoforms depends strongly upon DNA sequence and topology
Language English Country France Media print-electronic
Document type Journal Article
PubMed
36549455
DOI
10.1016/j.biochi.2022.12.011
PII: S0300-9084(22)00335-2
Knihovny.cz E-resources
- Keywords
- Atomic force microscopy, G-quadruplex, Supercoiled DNA, p53 isoforms, p53-DNA binding,
- MeSH
- Alternative Splicing * MeSH
- DNA genetics metabolism MeSH
- Humans MeSH
- Tumor Suppressor Protein p53 * metabolism MeSH
- Protein Isoforms genetics metabolism MeSH
- Base Sequence MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA MeSH
- Tumor Suppressor Protein p53 * MeSH
- Protein Isoforms MeSH
The p53 protein is a key tumor suppressor and the most commonly mutated and down-regulated protein in human tumors. It functions mainly through interaction with DNA, and p53 acts as a transcription factor that recognizes the so-called p53 target sites on the promoters of various genes. P53 has been shown to exist as many isoforms, including three C-terminal isoforms that are produced by alternative splicing. Because the C-terminal domain is responsible for sequence-nonspecific binding and regulation of p53 binding, we have analyzed DNA recognition by these C-terminal isoforms. Using atomic force microscopy, we show for the first time that all C-terminal isoforms recognize superhelical DNA. It is particularly noteworthy that a sequence-specific p53 consensus binding site is bound by p53α and β isoforms with similar affinities, whilst p53α shows higher binding to a quadruplex sequence than both p53β and p53γ, and p53γ loses preferential binding to both the consensus binding sequence and the quadruplex-forming sequence. These results show the important role of the variable p53 C-terminal amino acid sequences for DNA recognition.
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