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

0574514 - BFÚ 2024 RIV NL eng J - Článek v odborném periodiku
Goswami, Pratik - Šislerová, Lucie - Dobrovolná, Michaela - Havlík, J. - Šťastný, J. - Brázda, Václav
Interaction of C-terminal p53 isoforms depends strongly upon DNA sequence and topology.
Biochimie. Roč. 208, MAY 2023 (2023), s. 93-99. ISSN 0300-9084. E-ISSN 1638-6183
Grant CEP: GA ČR(CZ) GA22-21903S
Institucionální podpora: RVO:68081707
Klíčová slova: p53 isoforms * G-quadruplex * Atomic force microscopy * p53-DNA binding * Supercoiled DNA
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 3.9, rok: 2022
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S0300908422003352?via%3Dihub

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 p53a and b isoforms with similar affinities, whilst p53a shows higher binding to a quadruplex sequence than both p53b and p53g, and p53g 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. (c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
Trvalý link: https://hdl.handle.net/11104/0350064