Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells

Abstract The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process....

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Autores principales: Hanxiang Chen, Qishu Zhang, Lijun Qiao, Xueli Fan, Weifang Zhang, Weiming Zhao, Jason J. Chen
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/04b85512866f468bb2551c1476b8588a
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spelling oai:doaj.org-article:04b85512866f468bb2551c1476b8588a2021-12-02T11:40:51ZCdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells10.1038/s41598-017-03060-w2045-2322https://doaj.org/article/04b85512866f468bb2551c1476b8588a2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03060-whttps://doaj.org/toc/2045-2322Abstract The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia. Among differentially expressed proteins identified, Cdc6 is a DNA replication initiation factor and exhibits oncogenic activities when overexpressed. We have recently demonstrated that Cdc6 was required for E7-induced re-replication. Significantly, here we showed that Cdc6 played a role in E7-mediated G1 checkpoint abrogation under hypoxic condition, and the function could possibly be independent from its role in DNA replication initiation. This study uncovered a new function of Cdc6 in regulating cell cycle progression and has important implications in HPV-associated cancers.Hanxiang ChenQishu ZhangLijun QiaoXueli FanWeifang ZhangWeiming ZhaoJason J. ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hanxiang Chen
Qishu Zhang
Lijun Qiao
Xueli Fan
Weifang Zhang
Weiming Zhao
Jason J. Chen
Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells
description Abstract The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia. Among differentially expressed proteins identified, Cdc6 is a DNA replication initiation factor and exhibits oncogenic activities when overexpressed. We have recently demonstrated that Cdc6 was required for E7-induced re-replication. Significantly, here we showed that Cdc6 played a role in E7-mediated G1 checkpoint abrogation under hypoxic condition, and the function could possibly be independent from its role in DNA replication initiation. This study uncovered a new function of Cdc6 in regulating cell cycle progression and has important implications in HPV-associated cancers.
format article
author Hanxiang Chen
Qishu Zhang
Lijun Qiao
Xueli Fan
Weifang Zhang
Weiming Zhao
Jason J. Chen
author_facet Hanxiang Chen
Qishu Zhang
Lijun Qiao
Xueli Fan
Weifang Zhang
Weiming Zhao
Jason J. Chen
author_sort Hanxiang Chen
title Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells
title_short Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells
title_full Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells
title_fullStr Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells
title_full_unstemmed Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells
title_sort cdc6 contributes to abrogating the g1 checkpoint under hypoxic conditions in hpv e7 expressing cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/04b85512866f468bb2551c1476b8588a
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