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.

Original Title

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

Type

journal article in Web of Science

Language

English

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.

Keywords

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

Authors

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

Released

16. 12. 2022

ISBN

1638-6183

Periodical

BIOCHIMIE

Year of study

667

Number

červen

State

French Republic

Pages from

1

Pages to

7

Pages count

7

URL

https://www.sciencedirect.com/science/article/abs/pii/S0300908422003352?via%3Dihub

BibTex

@article{BUT180505,
  author="GOSWAMI, P. and ŠISLEROVÁ, L. and DOBROVOLNÁ, M. and HAVLÍK, J. and ŠŤASTNÝ, J. and BRÁZDA, V.",
  title="Interaction of C-terminal p53 isoforms depends strongly upon DNA sequence and topology",
  journal="BIOCHIMIE",
  year="2022",
  volume="667",
  number="červen",
  pages="1--7",
  doi="10.1016/j.biochi.2022.12.011",
  issn="1638-6183",
  url="https://www.sciencedirect.com/science/article/abs/pii/S0300908422003352?via%3Dihub"
}