Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy

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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
Journal Title:
Cell Cycle
Keywords:
Publication Date:
19 March 2015
Citation:
Chye Ling Tan, Sébastien Teissier, Jayantha Gunaratne, Ling Shih Quek& Sophie Bellanger (2015) Stranglehold on the spindle assembly checkpoint: the humanpapillomavirus E2 protein provokes BUBR1-dependent aneuploidy , Cell Cycle, 14:9, 1459-1470,DOI: 10.1080/15384101.2015.1021519
Abstract:
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.
License type:
http://creativecommons.org/licenses/by-nc/4.0/
Funding Info:
Description:
ISSN:
1538-4101
1551-4005
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