Mathematical Modeling of E6-p53 interactions in Cervical Cancer

Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, AI; Ullah, Mukhtar

doi:10.22034/APJCP.2017.18.4.1057

Mathematical Modeling of E6-p53 interactions in Cervical Cancer

Document Type : Research Articles

Authors

¹ Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad, Pakistan

² Department of Electronics Engineering, Capital University of Science and Technology, Islamabad, Pakistan

³ Department of Electrical Engineering, National University of Computer and Emerging Sciences, Islamabad, Pakistan.

10.22034/APJCP.2017.18.4.1057

Abstract

Background: Cervical cancer is the third most common cancer in women throughout the world. The human
papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant
protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development
of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. Insilico
simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for
its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results:
Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule
drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its
tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins.
Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule
drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using
CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available.
This strategy should play an effective role in the development of therapies against cancer.

Keywords