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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00574514" target="_blank" >RIV/68081707:_____/23:00574514 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62156489:43110/23:43922658 RIV/00216305:26210/22:PU146617

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0300908422003352?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0300908422003352?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biochi.2022.12.011" target="_blank" >10.1016/j.biochi.2022.12.011</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA22-21903S" target="_blank" >GA22-21903S: Lokální struktury DNA a jejich role ve funkci mutantního proteinu p53 z lidských nádorů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biochimie

ISSN

0300-9084

e-ISSN

1638-6183

Svazek periodika

208

Číslo periodika v rámci svazku

MAY 2023

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

7

Strana od-do

93-99

Kód UT WoS článku

001009864200001

EID výsledku v databázi Scopus

2-s2.0-85144931283