EconPapers    
Economics at your fingertips  
 

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

Klara Kohoutova, Pavel Srb, Veronika Obsilova (), Vaclav Veverka () and Tomas Obsil ()
Additional contact information
Klara Kohoutova: Charles University
Pavel Srb: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences
Veronika Obsilova: Division BIOCEV
Vaclav Veverka: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences
Tomas Obsil: Charles University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59106-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59106-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59106-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().

 
Page updated 2025-06-03
Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59106-5