Human papillomavirus (HPV) is the etiological agent for multiple forms of cancer

Question

Human papillomavirus (HPV) is the etiological agent for multiple forms of cancer, including cervical, oropharyngeal, penile and anal cancers. Of these, HPV-mediated cervical cancer is the most common. Primary HPV infection occurs in undifferentiated columnar cells of the cervical basal epithelium, the endocervix. Conversely, virions egress exclusively from terminally differentiated cells comprising the outer layer of the cervical epithelium, the ectocervix. Thus, the virus relies on proliferation and subsequent differentiation of endodermal cells up the cervical epithelial wall for the production of new virions. To ensure this process occurs, HPV encodes two proteins, E6 & E7, to inhibit apoptotic pathways and promote cellular proliferation, respectively. E6 binds to and inactivates p53 while E7 binds to and inactivates retinoblastoma protein. In over 80% of HPV-mediated cervical carcinomas, the viral genome integrates into the host genome. Ultimately, this causes unregulated production of oncoproteins E6 & E7 and cancer arises as a result of this overexpression.

Focus on deregulation of the cell cycle at the level of E7 promote cancer development/progression.

1) HPV protein E7 binds to and inactivates the retinoblastoma protein.

i) What is the normal cellular role of retinoblastoma (Rb) protein?

ii) How is Rb normally regulated in the cell (what turns it off/on)?

Explanation / Answer

1)
i) Ans-
             The cellular role of retinoblastoma protein is to inhibit the cell cycle progression from the G1 to the S phase. Rb protein performs by interacting with E2F transcription factors.
ii) Ans-
                    Retinoblastoma protein consists of a large and small pocket. The large pocket composed of both the small pocket and the C-terminal domain. Rb domains such as A and B are connected by a flexible linker that allows altering the pocket domain conformation. Cyclin-CDK phosphorylated the C-terminus and alter the conformation of Rb. As a result, inhibit the E2F binding and Rb itself is inactivated. In the inactivated form, E2F is unbound and transcribe genes to activate DNA synthesis. During the M-to-G1 transition, pRb is then dephosphorylated by PP1 and return to its growth-suppressive hypophosphorylated state Rb.

Related Questions

Navigate

• Browse (All)
• Browse H
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.