UMMS Affiliation
Department of Medicine
Publication Date
2018-06-12
Document Type
Article
Disciplines
Cancer Biology | Cell Biology | Immunology and Infectious Disease | Molecular Biology | Neoplasms
Abstract
Infection with high-risk human papillomaviruses (HR-HPVs, including HPV-16, HPV-18, HPV-31) plays a central aetiologic role in the development of cervical carcinoma. The transforming properties of HR-HPVs mainly reside in viral oncoproteins E6 and E7. E6 protein degrades the tumour suppressor p53 and abrogates cell cycle checkpoints. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is involved in the carcinogenesis of many human malignancies. Our previous data showed that CIP2A was overexpressed in cervical cancer. However, the regulation of CIP2A by HPV-16E6 remains to be elucidated. In this study, we demonstrated that HPV-16E6 significantly up-regulated CIP2A mRNA and protein expression in a p53-degradation-dependent manner. Knockdown of CIP2A by siRNA inhibited viability and DNA synthesis and caused G1 cell cycle arrest of 16E6-expressing cells. Knockdown of CIP2A resulted in a significant reduction in the expression of cyclin-dependent kinase 1 (Cdk1) and Cdk2. Although CIP2A has been reported to stabilize c-Myc by inhibiting PP2A-mediated dephosphorylation of c-Myc, we have presented evidence that the regulation of Cdk1 and Cdk2 by CIP2A is dependent on transcription factor B-Myb rather than c-Myc. Taken together, our study reveals the role of CIP2A in abrogating the G1 checkpoint in HPV-16E6-expressing cells and helps in understanding the molecular basis of HPV-induced oncogenesis.
Keywords
B-Myb, CIP2A, Cdk1, E6 oncoprotein, G1/S transition, human papillomavirus
Rights and Permissions
© 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
10.1111/jcmm.13693
Source
J Cell Mol Med. 2018 Jun 12. doi: 10.1111/jcmm.13693. Link to article on publisher's site
Journal/Book/Conference Title
Journal of cellular and molecular medicine
Related Resources
PubMed ID
29893470
Repository Citation
Tian Y, Chen H, Qiao L, Zhang W, Zheng J, Zhao W, Chen J, Zhang W. (2018). CIP2A facilitates the G1/S cell cycle transition via B-Myb in human papillomavirus 16 oncoprotein E6-expressing cells. Open Access Articles. https://doi.org/10.1111/jcmm.13693. Retrieved from https://escholarship.umassmed.edu/oapubs/3515
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cancer Biology Commons, Cell Biology Commons, Immunology and Infectious Disease Commons, Molecular Biology Commons, Neoplasms Commons