Cargando…

FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage

DNA damage as a result of environmental stress is recognized by sensor proteins that trigger repair mechanisms, or, if repair is unsuccessful, initiate apoptosis. Defects in DNA damage-induced apoptosis promote genomic instability and tumorigenesis. The protein ataxia-telangiectasia mutated (ATM) is...

Descripción completa

Detalles Bibliográficos
Autores principales: Chung, Young Min, Park, See-Hyoung, Tsai, Wen-Bin, Wang, Shih-Ya, Ikeda, Masa-Aki, Berek, Jonathan S., Chen, David J., Hu, Mickey C-T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589124/
https://www.ncbi.nlm.nih.gov/pubmed/22893124
http://dx.doi.org/10.1038/ncomms2008
_version_ 1782261695445467136
author Chung, Young Min
Park, See-Hyoung
Tsai, Wen-Bin
Wang, Shih-Ya
Ikeda, Masa-Aki
Berek, Jonathan S.
Chen, David J.
Hu, Mickey C-T.
author_facet Chung, Young Min
Park, See-Hyoung
Tsai, Wen-Bin
Wang, Shih-Ya
Ikeda, Masa-Aki
Berek, Jonathan S.
Chen, David J.
Hu, Mickey C-T.
author_sort Chung, Young Min
collection PubMed
description DNA damage as a result of environmental stress is recognized by sensor proteins that trigger repair mechanisms, or, if repair is unsuccessful, initiate apoptosis. Defects in DNA damage-induced apoptosis promote genomic instability and tumorigenesis. The protein ataxia-telangiectasia mutated (ATM) is activated by DNA double strand breaks and regulates apoptosis via p53. Here we show that FOXO3 interacts with the ATM-Chk2-p53 complex, augments phosphorylation of the complex and induces the formation of nuclear foci in cells upon DNA damage. FOXO3 is essential for DNA damage-induced apoptosis and conversely FOXO3 requires ATM, Chk2, and phosphorylated p53 isoforms to trigger apoptosis as a result of DNA damage. Under these conditions FOXO3 may also play a role in regulating chromatin retention of phosphorylated p53. These results suggest an essential link between FOXO3 and the ATM-Chk2-p53-mediated apoptotic program following DNA damage.
format Online
Article
Text
id pubmed-3589124
institution National Center for Biotechnology Information
language English
publishDate 2012
record_format MEDLINE/PubMed
spelling pubmed-35891242013-03-05 FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage Chung, Young Min Park, See-Hyoung Tsai, Wen-Bin Wang, Shih-Ya Ikeda, Masa-Aki Berek, Jonathan S. Chen, David J. Hu, Mickey C-T. Nat Commun Article DNA damage as a result of environmental stress is recognized by sensor proteins that trigger repair mechanisms, or, if repair is unsuccessful, initiate apoptosis. Defects in DNA damage-induced apoptosis promote genomic instability and tumorigenesis. The protein ataxia-telangiectasia mutated (ATM) is activated by DNA double strand breaks and regulates apoptosis via p53. Here we show that FOXO3 interacts with the ATM-Chk2-p53 complex, augments phosphorylation of the complex and induces the formation of nuclear foci in cells upon DNA damage. FOXO3 is essential for DNA damage-induced apoptosis and conversely FOXO3 requires ATM, Chk2, and phosphorylated p53 isoforms to trigger apoptosis as a result of DNA damage. Under these conditions FOXO3 may also play a role in regulating chromatin retention of phosphorylated p53. These results suggest an essential link between FOXO3 and the ATM-Chk2-p53-mediated apoptotic program following DNA damage. 2012 /pmc/articles/PMC3589124/ /pubmed/22893124 http://dx.doi.org/10.1038/ncomms2008 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chung, Young Min
Park, See-Hyoung
Tsai, Wen-Bin
Wang, Shih-Ya
Ikeda, Masa-Aki
Berek, Jonathan S.
Chen, David J.
Hu, Mickey C-T.
FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
title FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
title_full FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
title_fullStr FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
title_full_unstemmed FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
title_short FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
title_sort foxo3 signalling links atm to the p53 apoptotic pathway following dna damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589124/
https://www.ncbi.nlm.nih.gov/pubmed/22893124
http://dx.doi.org/10.1038/ncomms2008
work_keys_str_mv AT chungyoungmin foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage
AT parkseehyoung foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage
AT tsaiwenbin foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage
AT wangshihya foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage
AT ikedamasaaki foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage
AT berekjonathans foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage
AT chendavidj foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage
AT humickeyct foxo3signallinglinksatmtothep53apoptoticpathwayfollowingdnadamage