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Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response
Forkhead box F1 (Foxf1) transcription factor is an important regulator of embryonic development but its role in tumor cells remains incompletely understood. While 16 proteins were characterized in Fanconi anemia (FA) core complex, its interactions with cellular transcriptional machinery remain poorl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811506/ https://www.ncbi.nlm.nih.gov/pubmed/26625197 |
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author | Pradhan, Arun Ustiyan, Vladimir Zhang, Yufang Kalin, Tanya V. Kalinichenko, Vladimir V. |
author_facet | Pradhan, Arun Ustiyan, Vladimir Zhang, Yufang Kalin, Tanya V. Kalinichenko, Vladimir V. |
author_sort | Pradhan, Arun |
collection | PubMed |
description | Forkhead box F1 (Foxf1) transcription factor is an important regulator of embryonic development but its role in tumor cells remains incompletely understood. While 16 proteins were characterized in Fanconi anemia (FA) core complex, its interactions with cellular transcriptional machinery remain poorly characterized. Here, we identified FoxF1 protein as a novel interacting partner of the FA complex proteins. Using multiple human and mouse tumor cell lines and Foxf1(+/−) mice we demonstrated that FoxF1 physically binds to and increases stability of FA proteins. FoxF1 co-localizes with FANCD2 in DNA repair foci in cultured cells and tumor tissues obtained from cisplatin-treated mice. In response to DNA damage, FoxF1-deficient tumor cells showed significantly reduced FANCD2 monoubiquitination and FANCM phosphorylation, resulting in impaired formation of DNA repair foci. FoxF1 knockdown caused chromosomal instability, nuclear abnormalities, and increased tumor cell death in response to DNA-damaging agents. Overexpression of FoxF1 in DNA-damaged cells improved stability of FA proteins, decreased chromosomal and nuclear aberrations, restored formation of DNA repair foci and prevented cell death after DNA damage. These findings demonstrate that FoxF1 is a key component of FA complexes and a critical mediator of DNA damage response in tumor cells. |
format | Online Article Text |
id | pubmed-4811506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48115062016-04-25 Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response Pradhan, Arun Ustiyan, Vladimir Zhang, Yufang Kalin, Tanya V. Kalinichenko, Vladimir V. Oncotarget Research Paper Forkhead box F1 (Foxf1) transcription factor is an important regulator of embryonic development but its role in tumor cells remains incompletely understood. While 16 proteins were characterized in Fanconi anemia (FA) core complex, its interactions with cellular transcriptional machinery remain poorly characterized. Here, we identified FoxF1 protein as a novel interacting partner of the FA complex proteins. Using multiple human and mouse tumor cell lines and Foxf1(+/−) mice we demonstrated that FoxF1 physically binds to and increases stability of FA proteins. FoxF1 co-localizes with FANCD2 in DNA repair foci in cultured cells and tumor tissues obtained from cisplatin-treated mice. In response to DNA damage, FoxF1-deficient tumor cells showed significantly reduced FANCD2 monoubiquitination and FANCM phosphorylation, resulting in impaired formation of DNA repair foci. FoxF1 knockdown caused chromosomal instability, nuclear abnormalities, and increased tumor cell death in response to DNA-damaging agents. Overexpression of FoxF1 in DNA-damaged cells improved stability of FA proteins, decreased chromosomal and nuclear aberrations, restored formation of DNA repair foci and prevented cell death after DNA damage. These findings demonstrate that FoxF1 is a key component of FA complexes and a critical mediator of DNA damage response in tumor cells. Impact Journals LLC 2015-11-28 /pmc/articles/PMC4811506/ /pubmed/26625197 Text en Copyright: © 2016 Pradhan et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Pradhan, Arun Ustiyan, Vladimir Zhang, Yufang Kalin, Tanya V. Kalinichenko, Vladimir V. Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response |
title | Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response |
title_full | Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response |
title_fullStr | Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response |
title_full_unstemmed | Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response |
title_short | Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response |
title_sort | forkhead transcription factor foxf1 interacts with fanconi anemia protein complexes to promote dna damage response |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811506/ https://www.ncbi.nlm.nih.gov/pubmed/26625197 |
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