Lecture 10 - Papova 4

Question 1

What is Merkcel cell carcinoma?

Answer 1

A rare, highly metastatic skin cancer.

Question 2

Name the technique used to discover Merkel Cell Carcinoma Virus

Answer 2

Digital Transcriptome Subtraction

Question 3

How does digital transcriptome subtraction work?

Answer 3

Infected tissue is first treated to remove human DNA. Then a cDNA library is made from the total RNA extracted from the tissue. Bioinformatics is used to compare all cDNA to human genome, ID new sequences and then compare them to all known pathogen sequences in the library.

Question 4

What are the 2 main features of MCV in MCC? (what happens to the genome?)

Answer 4

• Partial viral genome integration (80% of MCC have viral integration in cancer cells)
• loss of viral structural genes

Question 5

What happens to the LT gene when it is integrated during cell transformation?

Answer 5

It loses its helicase activity

Question 6

What are the 2 MCV antigens involved in MCC? Which one can induce transformation on its own and which one cant?

Answer 6

LTAg: can’t induce cell transformation on its own

sTAg: can induce cell transformation on its own

Question 7

What tumor suppressor does MCV LTAg interact with?

Answer 7

LTAg binds with Rb to induce cell cycle

Question 8

Which tumor suppressor does MCV LTAg not interact with that it does in other papova viruses?

Answer 8

LTAg does not interact with p53 (unlike SV40)

Question 9

Describe how sTAg can cause cell transformation (name proteins involved and their function)

Answer 9

elF4E is a activator of cap-dependent translation. 4E-BP prevents elF4E from binding the 5’ cap of mRNA. When 4E-BP is phosphorylated, it releases elF4E which can initiate translation. sTAg keeps 4E-BP phosphorylated and thus increases cap-dependent translation.