Human papillomavirus E7 induces p63 expression to modulate DNA damage response.
AffiliationDivision of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester Cancer Research Centre, Wilmslow Road, Manchester, M20 4QL, UK
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AbstractCervical cancer is the third most common malignancy diagnosed in women worldwide. The major aetiological factor underlying the malignant transformation of cervical cells is the persistent infection with high-risk human papillomaviruses (HR-HPV), with more than 99% of cases expressing viral sequences. Here, we report a previously unknown mechanism driven by high-risk human papillomavirus E7 protein to modulate response to DNA damage in cervical cancer cells. Our data shows that HR-HPV E7 oncoprotein induces the transcription of the p53-family member p63, which modulates DNA damage response pathways, to facilitate repair of DNA damage. Based on our findings, we proposed a model, where HR-HPV could interfere with the sensitivity of transformed cells to radiation therapy by modulating DNA damage repair efficiency. Importantly, we have shown for the first time a critical role for p63 in response to DNA damage in cervical cancer cells.
CitationHuman papillomavirus E7 induces p63 expression to modulate DNA damage response. 2018, 9 (2):127 Cell Death Dis
JournalCell Death & Disease
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