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

The result's identifiers

  • Result code in 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>

  • Alternative codes found

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

  • Result on the web

    <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>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2025

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Nature Communications

  • ISSN

    2041-1723

  • e-ISSN

    2041-1723

  • Volume of the periodical

    16

  • Issue of the periodical within the volume

    27 May

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    12

  • Pages from-to

    4907

  • UT code for WoS article

    001497890700031

  • EID of the result in the Scopus database

    2-s2.0-105006828567