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Human papillomavirus E7 induces p63 expression to modulate DNA damage response.
Eldakhakhny, Sahar Zhou, Qing Crosbie, Emma J Sayan, Berna S
Eldakhakhny, Sahar
Zhou, Qing
Crosbie, Emma J
Sayan, Berna S
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Abstract
Cervical 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.
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2018-01-26
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Human papillomavirus E7 induces p63 expression to modulate DNA damage response. 2018, 9 (2):127 Cell Death Dis