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FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA
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SYSNO ASEP 0556576 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA Author(s) Mandal, R. (CZ)
Kohoutová, Klára (FGU-C) ORCID
Petrvalská, Olivia (FGU-C) RID, ORCID, SAI
Horváth, M. (CZ)
Srb, Pavel (UOCHB-X) RID, ORCID
Veverka, Václav (UOCHB-X) RID, ORCID
Obšilová, Veronika (FGU-C) RID, ORCID, SAI
Obšil, Tomáš (FGU-C) RID, ORCIDArticle number e4287 Source Title Protein Science. - : Wiley - ISSN 0961-8368
Roč. 31, č. 5 (2022)Number of pages 13 s. Language eng - English Country US - United States Keywords DNA binding ; forkhead box O 4 ; nuclear magnetic resonance ; protein-protein interaction ; senescence ; transcription factor p53 OECD category Biochemistry and molecular biology R&D Projects GA21-02080S GA ČR - Czech Science Foundation (CSF) Research Infrastructure CIISB II - 90127 - Masarykova univerzita Method of publishing Limited access Institutional support FGU-C - RVO:67985823 ; UOCHB-X - RVO:61388963 UT WOS 000788245500005 EID SCOPUS 85129098228 DOI 10.1002/pro.4287 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://doi.org/10.1002/pro.4287
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