Human papillomavirus E7 induces p63 expression to modulate DNA damage response

Eldakhakhny, S; Zhou, Q; Crosbie, EJ; Sayan, BS

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.

Citation

Eldakhakhny, S., Zhou, Q., Crosbie, E., & Sayan, B. (2018). Human papillomavirus E7 induces p63 expression to modulate DNA damage response. Cell Death and Disease, 9, https://doi.org/10.1038/s41419-017-0149-6

• Journal Article Type: Article
• Acceptance Date: Nov 15, 2017
• Online Publication Date: Jan 26, 2018
• Publication Date: Jan 26, 2018
• Deposit Date: Feb 14, 2023
• Publicly Available Date: Feb 14, 2023
• Journal: Cell Death and Disease
• Publisher: Nature Publishing Group
• Volume: 9
• DOI: https://doi.org/10.1038/s41419-017-0149-6
• Publisher URL: https://doi.org/10.1038/s41419-017-0149-6