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Tumor suppressor p16 INK4A is necessary for survival of cervical carcinoma cell lines
Abstract
Significance: Here we report that addiction to histone lysine demethylase (KDM)6B expression is shared by a number of cervical carcinoma lines and arises as a direct and immediate consequence of human papillomavirus (HPV)16 E7 oncoprotein expression. We also report that the p16 INK4A tumor suppressor is a mediator of KDM6B addiction and that p16 expression is necessary for survival of HPV E7-expressing cells. The addiction of p16 INK4A is based on its ability to inhibit CDK4/CDK6 activity. We also present data that KDM6 inhibition may be evaluated as a therapeutic modality for high-risk HPV-associated lesions and cancers.
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“KDM6B induction mediates increased expression of the cervical cancer biomarker p16INK4A. Higher expression of p16INK4A caused by HPV-16 E7 mediated KDM6D upregulation represents an E7-triggered oncogene-induced senescence (OIS) response.”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [333]
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“HPVs have evolved to target pRB for ubiquitin-dependent proteasomal degradation, which is why p16INK4A upregulation in HPV-positive cancer cells does not inhibit proliferation [332,333,334]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [333]
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Cites
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Cited by
Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 INK4a ) in Cancer
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Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Metadata
- Authors
- McLaughlin-Drubin, M. E., Park, D., & Munger, K.
- Affiliations
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA 02115; and
- Committee on Virology,
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-09-17
- Volume
- 110
- Issue
- 40
- Pages
- 16175-16180
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 163
- References
- 9
- Language
- en
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