Human papillomavirus (HPV) is the etiological agent for multipleforms of cancer, including cervical, oropharyngeal, penile and analcancers. Of these, HPV-mediated cervical cancer is the most common.Primary HPV infection occurs in undifferentiated columnar cells ofthe cervical basal epithelium, the endocervix. Conversely, virionsegress exclusively from terminally differentiated cells comprisingthe outer layer of the cervical epithelium, the ectocervix. Thus,the virus relies on proliferation and subsequent differentiation ofendodermal cells up the cervical epithelial wall for the productionof new virions. To ensure this process occurs, HPV encodes twoproteins, E6 & E7, to inhibit apoptotic pathways and promotecellular proliferation, respectively. E6 binds to and inactivatesp53 while E7 binds to and inactivates retinoblastoma protein. Inover 80% of HPV-mediated cervical carcinomas, the viral genomeintegrates into the host genome. Ultimately, this causesunregulated production of oncoproteins E6 & E7 and cancerarises as a result of this overexpression.

d) What would be the result of p53 inactivation with respect tothe cell cycle?

e) P53 not only has a role in the DNA damage response but alsoin the intrinsic apoptotic pathway. Explain how p53 can promoteactivation of the intrinsic apoptotic pathway.