Structural plasticity of the FOXO-DBD:p53-TAD interaction

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00635728" target="_blank" >RIV/61388963:_____/25:00635728 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/25:00635728 RIV/00216208:11310/25:10498607

Výsledek na webu

<a href="https://doi.org/10.1038/s41467-025-59106-5" target="_blank" >https://doi.org/10.1038/s41467-025-59106-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-025-59106-5" target="_blank" >10.1038/s41467-025-59106-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structural plasticity of the FOXO-DBD:p53-TAD interaction

Popis výsledku v původním jazyce

The transcription factors FOXO4 and p53 regulate aging, and their deregulation has been linked to several diseases, including cancer. Under stress conditions, cellular senescence is promoted by p53 sequestration and senescence-associated protein p21 transcriptional upregulation induced by interactions between the FOXO4 Forkhead DNA-binding domain and the p53 transactivation domain. However, the molecular details of these interactions remain unclear. Here, we report that these interactions between p53 and FOXO4 domains are highly heterogeneous. The p53 transactivation domain primarily interacts with the region formed by the N-terminal helical bundle of the FOXO4 Forkhead domain but retains a substantial degree of flexibility in the complex. In addition, NMR data-driven molecular simulations suggest that p53 interacts with FOXO4 through multiple binding modes. Overall, our findings not only provide the structural insights into interactions between FOXO4 and p53 but also highlight their potential as targets for developing senolytic compounds.

Název v anglickém jazyce

Structural plasticity of the FOXO-DBD:p53-TAD interaction

Popis výsledku anglicky

The transcription factors FOXO4 and p53 regulate aging, and their deregulation has been linked to several diseases, including cancer. Under stress conditions, cellular senescence is promoted by p53 sequestration and senescence-associated protein p21 transcriptional upregulation induced by interactions between the FOXO4 Forkhead DNA-binding domain and the p53 transactivation domain. However, the molecular details of these interactions remain unclear. Here, we report that these interactions between p53 and FOXO4 domains are highly heterogeneous. The p53 transactivation domain primarily interacts with the region formed by the N-terminal helical bundle of the FOXO4 Forkhead domain but retains a substantial degree of flexibility in the complex. In addition, NMR data-driven molecular simulations suggest that p53 interacts with FOXO4 through multiple binding modes. Overall, our findings not only provide the structural insights into interactions between FOXO4 and p53 but also highlight their potential as targets for developing senolytic compounds.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

2041-1723

Svazek periodika

16

Číslo periodika v rámci svazku

27 May

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

4907

Kód UT WoS článku

001497890700031

EID výsledku v databázi Scopus

2-s2.0-105006828567