Molecular simulation oF MDM2 and E6AP proteins as P53 regulator in cervical cancer

Abstract

Cervical cancer is a type of cancer characterized by abnormal cell growth in the cervical area. One of the main events that happen during tumorigenesis is the inactivation or degradation of the genome guardian, P53. Under normal circumstances, P53 is regulated by MDM2 protein. MDM2 can transfer ubiquitin to the transactivation domain of P53, targeting it for degradation by proteasomes. However, in the presence of HPV, HPV-E6 can utilize cellular E6AP to perform P53 degradation through the ubiquitin ligase mechanism. We validated both interactions through molecular docking in ClusPro. We also checked their normalized expression level in The Cancer Genomic Atlas (TCGA) using TCGA-Assembler. We found out both interactions are highly likely due to the spontaneity of the reaction indicated by the low free energy. MDM2 is overexpressed in cervical cancer cells, but E6AP expression is relatively constant. This indicates that the MDM2-mediated pathway is still sustained in cervical cancer cells. But since E6AP-mediated pathway is finally activated due to the presence of HPV-E6, both pathways may happen simultaneously. Further research is needed to confirm both pathways existence in cervical cancer cells and how they may coincide and affect each other.