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FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA
R. Mandal, K. Kohoutova, O. Petrvalska, M. Horvath, P. Srb, V. Veverka, V. Obsilova, T. Obsil
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1992 to 1 year ago
PubMed Central
from 1992 to 1 year ago
Europe PubMed Central
from 1992 to 1 year ago
Medline Complete (EBSCOhost)
from 2010-01-01 to 1 year ago
Wiley Free Content
from 1996 to 1 year ago
PubMed
35481640
DOI
10.1002/pro.4287
Knihovny.cz E-resources
- MeSH
- DNA chemistry MeSH
- Forkhead Transcription Factors * chemistry genetics metabolism MeSH
- Tumor Suppressor Protein p53 * genetics metabolism MeSH
- Cell Cycle Proteins metabolism MeSH
- Protein Binding MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
References provided by Crossref.org
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