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FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00556576" target="_blank" >RIV/61388963:_____/22:00556576 - isvavai.cz</a>

  • Alternative codes found

    RIV/67985823:_____/22:00556576 RIV/00216208:11310/22:10446733 RIV/00216224:14740/22:00128772

  • Result on the web

    <a href="https://doi.org/10.1002/pro.4287" target="_blank" >https://doi.org/10.1002/pro.4287</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1002/pro.4287" target="_blank" >10.1002/pro.4287</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA

  • Original language description

    Transcription factor p53 protects cells against tumorigenesis when subjected to various cellular stresses. Under these conditions, p53 interacts with transcription factor Forkhead box O (FOXO) 4, thereby inducing cellular senescence by upregulating the transcription of senescence-associated protein p21. However, the structural details of this interaction remain unclear. Here, we characterize the interaction between p53 and FOXO4 by NMR, chemical cross-linking, and analytical ultracentrifugation. Our results reveal that the interaction between p53 TAD and the FOXO4 Forkhead domain is essential for the overall stability of the p53:FOXO4 complex. Furthermore, contacts involving the N-terminal segment of FOXO4, the C-terminal negative regulatory domain of p53 and the DNA-binding domains of both proteins stabilize the complex, whose formation blocks p53 binding to DNA but without affecting the DNA-binding properties of FOXO4. Therefore, our structural findings may help to understand the intertwined functions of p53 and FOXO4 in cellular homeostasis, longevity, and stress response.

  • 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

    <a href="/en/project/GA21-02080S" target="_blank" >GA21-02080S: Molecular basis of interaction between FOXO Forkhead transcription factors and tumor suppressor p53</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2022

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Protein Science

  • ISSN

    0961-8368

  • e-ISSN

    1469-896X

  • Volume of the periodical

    31

  • Issue of the periodical within the volume

    5

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    13

  • Pages from-to

    e4287

  • UT code for WoS article

    000788245500005

  • EID of the result in the Scopus database

    2-s2.0-85129098228