Publication detail

Interaction of C-terminal p53 isoforms depends strongly upon DNA sequence and topology

GOSWAMI, P. ŠISLEROVÁ, L. DOBROVOLNÁ, M. HAVLÍK, J. ŠŤASTNÝ, J. BRÁZDA, V.

English title

Interaction of C-terminal p53 isoforms depends strongly upon DNA sequence and topology

Type

journal article in Web of Science

Language

en

Original abstract

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.

English abstract

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.

Keywords in English

p53 isoforms, G-quadruplex, Atomic force microscopy, p53-DNA binding, Supercoiled DNA

Released

16.12.2022

ISSN

1638-6183

Volume

667

Number

červen

Pages from–to

1–7

Pages count

7

BIBTEX


@article{BUT180505,
  author="Pratik {Goswami} and Lucie {Šislerová} and Michaela {Dobrovolná} and Jiří {Šťastný} and Václav {Brázda},
  title="Interaction of C-terminal p53 isoforms depends strongly upon DNA sequence and topology",
  year="2022",
  volume="667",
  number="červen",
  month="December",
  pages="1--7",
  issn="1638-6183"
}