THE EPIGENETIC REGULATION OF PEPTIDYLARGININE DEIMINASE 4 AND ASSOCIATED CELLULAR RESPONSE PATHWAYS GIVE INSIGHT INTO NOVEL CANCER THERAPEUTICS

Open Access
Author:
Radaoui, Alexander Brown
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Yanking Wang, Thesis Supervisor
  • David Scott Gilmour, Honors Advisor
  • Scott Brian Selleck, Faculty Reader
Keywords:
  • Cancer
  • PAD4
  • Epigenetics
  • CRISPR-Cas9
  • Molecular Cloning
Abstract:
PAD4 is a protein found in the nucleus of many cells that promote post-translational modification of arginine residues on histones and other nuclear transcription factors. By modifying arginine residues to citrulline through deamination reactions, the transcription of specific genes might be turned on or off that are required for proper cellular function. This regulatory mechanism can provide insight into the maintenance and preservation of homeostatic epigenetics inside the cell. In addition, PAD4 has been known to corepress the cell cycle check point regulator p53, affecting its role in conserving proper cellular growth and proliferation. The link between the loss of p53 function in malignant tumors and overexpression of PAD4 has potential in providing significant knowledge into cancer biology. The purpose of my experimentation is to compile research regarding the epigenetic regulation of PAD4 on cellular homeostasis by analyzing a variety of tumor suppressor genes. I would like to know what PAD4’s role is in regulating cell cycle signals. Through the research and techniques I have accumulated over the past two and a half years, I hope to show insightful data by implementing a PAD4 knockout plasmid into U2OS cells through CRISPR-Cas9 biotechnology, as well as perform qualitative PCR on treated SMAD3 knockout cells in order to better understand cellular maintenance signaling. Furthering the scientific communities knowledge of epigenetics is paramount in understanding prevalent immunological models like cancer and providing insight into possible drug design targets that can mitigate the effects of these diseases.