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Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy
The Human Papillomavirus (HPV) E2 protein, which inhibits the E6 and E7 viral oncogenes, is believed to have anti-oncogenic properties. Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614697/ https://www.ncbi.nlm.nih.gov/pubmed/25789401 http://dx.doi.org/10.1080/15384101.2015.1021519 |
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author | Tan, Chye Ling Teissier, Sébastien Gunaratne, Jayantha Quek, Ling Shih Bellanger, Sophie |
author_facet | Tan, Chye Ling Teissier, Sébastien Gunaratne, Jayantha Quek, Ling Shih Bellanger, Sophie |
author_sort | Tan, Chye Ling |
collection | PubMed |
description | The Human Papillomavirus (HPV) E2 protein, which inhibits the E6 and E7 viral oncogenes, is believed to have anti-oncogenic properties. Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy. This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. While BUBR1 silencing rescues the mitotic phenotype induced by E2, p53 silencing or presence of E6/E7 (inactivating p53 and increasing BUBR1 levels respectively) both amplify it. This work pinpoints E2 as a key protein in the initiation of HPV-induced cervical cancer and identifies the SAC as a target for oncogenic pathogens. Moreover, our results suggest a role of p53 in regulating the mitotic process itself and highlight SAC over-activation in a p53-negative context as a highly pathogenic event. |
format | Online Article Text |
id | pubmed-4614697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-46146972016-02-03 Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy Tan, Chye Ling Teissier, Sébastien Gunaratne, Jayantha Quek, Ling Shih Bellanger, Sophie Cell Cycle Report The Human Papillomavirus (HPV) E2 protein, which inhibits the E6 and E7 viral oncogenes, is believed to have anti-oncogenic properties. Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy. This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. While BUBR1 silencing rescues the mitotic phenotype induced by E2, p53 silencing or presence of E6/E7 (inactivating p53 and increasing BUBR1 levels respectively) both amplify it. This work pinpoints E2 as a key protein in the initiation of HPV-induced cervical cancer and identifies the SAC as a target for oncogenic pathogens. Moreover, our results suggest a role of p53 in regulating the mitotic process itself and highlight SAC over-activation in a p53-negative context as a highly pathogenic event. Taylor & Francis 2015-03-19 /pmc/articles/PMC4614697/ /pubmed/25789401 http://dx.doi.org/10.1080/15384101.2015.1021519 Text en © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Report Tan, Chye Ling Teissier, Sébastien Gunaratne, Jayantha Quek, Ling Shih Bellanger, Sophie Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy |
title | Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy |
title_full | Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy |
title_fullStr | Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy |
title_full_unstemmed | Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy |
title_short | Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy |
title_sort | stranglehold on the spindle assembly checkpoint: the human papillomavirus e2 protein provokes bubr1-dependent aneuploidy |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614697/ https://www.ncbi.nlm.nih.gov/pubmed/25789401 http://dx.doi.org/10.1080/15384101.2015.1021519 |
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