Lecture 8 - Papova 2 Flashcards
What percentage of cancers are caused by viruses?
20%
What are 3 ways LTAg ellicits cell transformation?
- inactivation of Rb
- inactivation of p53
- binding to Hsp70 (to assist in folding of capsid proteins)
What are 2 ways SV40 overcomes the monocistronic constraint of its eukarotic host cell?
- alternative splicing of viral pre-mRNA
- leaky scanning of mRNA (multiple translation start sites on single mRNA)
What is the difference between transformation and oncogenesis?
Transformation is a change in cell growth, phenotype or indefinite reproduction of the cells caused by the virus through introduction of inheritable viral genetic info
Oncogenesis is the transformation of a normal cell into a cancer cell
What do proto-oncogenes do?
They start the cell cycle
What do tumor suppressor genes do?
they have a dampening effect on regulation of the cell cycle or promote apoptosis or both
What 2 host tumor suppressor proteins does SV40 LTAg inhibit to initiate S phase?
Rb and p53
How does SV40 get around tumor suppressor protein Rb (retinoblastoma protein)?
Under normal conditions, Rb is bound to E2f. E2f is an transcriptional activator of S phase, Rb inhibits E2f. When viral LTAg is introduced, it binds Rb which then releases E2f. E2f is now able to induce S phase.
What are the 2 oncoproteins made by HPV and how do they inhibit the 2 tumor suppressor proteins already discussed?
E6 targets p53 for proteosomal degradation
E7 sequesters Rb from E2f
What is the function of Rb?
It is a tumor suppressor protein that inhibits the S phase transcriptional activator, E2f
What is the function of p53?
It is a tumor suppressor protein that can activate DNA repair enzymes, arrest the cell cycle and induce apoptosis
What is the difference between the action of HPV oncoprotein E6 and SV40 LTAg on p53?
E6 targets p53 for proteosomal degradation
LTAg sequesters p53
