ArticlePLoS pathogens2017
KDM6A addiction of cervical carcinoma cell lines is triggered by E7 and mediated by p21CIP1 suppression of replication stress.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Inhibition of high risk HPV31 E8^E2 repressor activity enables differentiation-independent genome amplification and E4 expression.PLoS pathogens · 2026Article
- Prevalence of KDM6A deficiency in human cancer: A tissue microarray study on 18,570 cancers from 153 different tumor types.Virchows Archiv : an international journal of pathology · 2026Article
- An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance.Cancers · 2026Review
- Advances in understanding the mechanisms of the human papillomavirus oncoproteins.Biochemical Society transactions · 2025Review
- EZH2 regulates tumor-associated macrophages by the KDM6A-mediated inflammatory response in HPV16-positive cervical cancer.Human cell · 2025Article
- E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer.Oncogene · 2024Article
- Unveiling the Molecular Landscape of Pancreatic Ductal Adenocarcinoma: Insights into the Role of the COMPASS-like Complex.International journal of molecular sciences · 2024Review
- Recombinant adenoviruses expressing HPV16/18 E7 upregulate the HDAC6 and DNMT3B genes in C33A cells.Frontiers in cellular and infection microbiology · 2024Article
- Review
- Molecular pathways in the development of HPV-induced oropharyngeal cancer.Cell communication and signaling : CCS · 2023Article
- For Better or Worse: Modulation of the Host DNA Damage Response by Human Papillomavirus.Annual review of virology · 2023Review
- HPV 16 E7 alters translesion synthesis signaling.Virology journal · 2022Article
- HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management.Nature reviews. Clinical oncology · 2022Review
- EGFR transcriptionally upregulates UTX via STAT3 in non-small cell lung cancer.Journal of cancer research and clinical oncology · 2022Article
- The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis.Viruses · 2021Review
- The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation.The Journal of general virology · 2021Review
- KDM6 Demethylases and Their Roles in Human Cancers.Frontiers in oncology · 2021Review
- Lysine Demethylases: Promising Drug Targets in Melanoma and Other Cancers.Frontiers in genetics · 2021Review
- Article
- Epigenetic Regulation of the Human Papillomavirus Life Cycle.Pathogens (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of E7 proteins encoded by carcinogenic, high-risk human papillomaviruses (HPVs) triggers increased expression of the histone H3 lysine 27 demethylase KDM6A. KDM6A expression is necessary for survival of high-risk HPV E7 expressing cells, including several cervical cancer lines. Here we show that increased KDM6A in response to high-risk HPV E7 expression causes epigenetic de-repression of the cell cycle and DNA replication inhibitor p21CIP1, and p21CIP1 expression is necessary for survival of high-risk HPV E7 expressing cells. The requirement for KDM6A and p21CIP1 expression for survival of high-risk HPV E7 expressing cells is based on p21CIP1's ability to inhibit DNA replication through PCNA binding. We show that ectopic expression of cellular replication factors can rescue the loss of cell viability in response to p21CIP1 and KDM6A depletion. Moreover, we discovered that nucleoside supplementation will override the loss of cell viability in response to p21CIP1 depletion, suggesting that p21CIP1 depletion causes lethal replication stress. This model is further supported by increased double strand DNA breaks upon KDM6A or p21CIP1 depletion and DNA combing experiments that show aberrant re-replication upon KDM6A or p21CIP1 depletion in high-risk HPV E7 expressing cells. Therefore, KDM6A and p21CIP1 expression are essential to curb E7 induced replication stress to levels that do not markedly interfere with cell viability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.