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

J 2022

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

MANDAL, Raju, Klara KOHOUTOVA, Olivia PETRVALSKA, Matej HORVATH, Pavel SRB et. al.

Basic information

Original name

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

Authors

MANDAL, Raju, Klara KOHOUTOVA, Olivia PETRVALSKA, Matej HORVATH, Pavel SRB, Vaclav VEVERKA, Veronika OBSILOVA and Tomas OBSIL

Edition

Protein Science, HOBOKEN, JOHN WILEY & SONS INC, 2022, 0961-8368

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.000

RIV identification code

RIV/00216224:14740/22:00128772

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1002/pro.4287

UT WoS

000788245500005

Keywords in English

DNA binding; Forkhead box O 4; nuclear magnetic resonance; protein-protein interaction; senescence; transcription factor p53

Abstract

V originále

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.

Links

90127, large research infrastructures

Name: CIISB II

Citovat

MANDAL, Raju, Klara KOHOUTOVA, Olivia PETRVALSKA, Matej HORVATH, Pavel SRB, Vaclav VEVERKA, Veronika OBSILOVA and Tomas OBSIL. FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA. Protein Science. HOBOKEN: JOHN WILEY & SONS INC, 2022, vol. 31, No 5, p. 1-13. ISSN 0961-8368. Available from: https://dx.doi.org/10.1002/pro.4287.

@article{2262447,
   author = {Mandal, Raju and Kohoutova, Klara and Petrvalska, Olivia and Horvath, Matej and Srb, Pavel and Veverka, Vaclav and Obsilova, Veronika and Obsil, Tomas},
   article_location = {HOBOKEN},
   article_number = {5},
   doi = {http://dx.doi.org/10.1002/pro.4287},
   keywords = {DNA binding; Forkhead box O 4; nuclear magnetic resonance; protein-protein interaction; senescence; transcription factor p53},
   language = {eng},
   issn = {0961-8368},
   journal = {Protein Science},
   title = {FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA},
   url = {https://onlinelibrary.wiley.com/doi/10.1002/pro.4287},
   volume = {31},
   year = {2022}
}

TY  - JOUR
ID  - 2262447
AU  - Mandal, Raju - Kohoutova, Klara - Petrvalska, Olivia - Horvath, Matej - Srb, Pavel - Veverka, Vaclav - Obsilova, Veronika - Obsil, Tomas
PY  - 2022
TI  - FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA
JF  - Protein Science
VL  - 31
IS  - 5
SP  - 1-13
EP  - 1-13
PB  - JOHN WILEY & SONS INC
SN  - 09618368
KW  - DNA binding
KW  - Forkhead box O 4
KW  - nuclear magnetic resonance
KW  - protein-protein interaction
KW  - senescence
KW  - transcription factor p53
UR  - https://onlinelibrary.wiley.com/doi/10.1002/pro.4287
N2  - 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.
ER  -

MANDAL, Raju, Klara KOHOUTOVA, Olivia PETRVALSKA, Matej HORVATH, Pavel SRB, Vaclav VEVERKA, Veronika OBSILOVA and Tomas OBSIL. FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA. \textit{Protein Science}. HOBOKEN: JOHN WILEY \&{}amp; SONS INC, 2022, vol.~31, No~5, p.~1-13. ISSN~0961-8368. Available from: https://dx.doi.org/10.1002/pro.4287.

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