Question

Pick two DNA tumor viruses (adenovirus and HPV)and briefly explain how their respective oncoproteins directly interfere with the function of Retinoblastoma protein (pRb), or p53, or both. Make an illustration to help your explanation.

Answer 1

The adenoviruses are a large family of DNA viruses with genomes of about 35 kb. The adenoviruses are not associated with naturally occurring cancers in either humans or other animals. However, they are widely studied and important models in experimental cancer biology.

Like SV40 and polyomaviruses, the adenoviruses are lytic in cells of their natural host species, but can induce transformation in nonpermissive hosts. Transformation by the adenoviruses results from expression of two early genes, E1A and E1B, which are required for virus replication in permissive cells . These transforming proteins inactivate the Rb and p53 tumor suppressor proteins, with E1A binding to Rb and E1B binding to p53. It thus appears that SV40, papillomaviruses, and adenoviruses all induce transformation by a common pathway, in which altering regulation of the cell cycle by interfering with the activities of Rb and p53 plays a central role.

Human Papilloma viruses

The papillomaviruses are small DNA viruses (genomes of approximately 8 kb) that induce both benign and malignant tumors in humans and a variety of other animal species. Approximately 60 different types of human papillomaviruses, which infect epithelial cells of several tissues, have been identified. Some of these viruses cause only benign tumors (such as warts), whereas others are causative agents of malignant carcinomas, particularly cervical and other anogenital cancers. The mortality from cervical cancer is relatively low in the United States, in large part as a result of early detection and curative treatment made possible by the Pap smear. In other parts of the world, however, cervical cancer remains common; it is responsible for 5 to 10% of worldwide cancer incidence.

Cell transformation by human papillomaviruses results from expression of two early-region genes, E6 and E7 .The E6 and E7 proteins act analogously to SV40 T antigen by interfering with the function of the cellular Rb and p53 proteins. In particular, E7 binds to Rb, and E6 stimulates the degradation of p53 by ubiquitin-mediated proteolysis.