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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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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 |
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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 |
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