Lecture 9 - Papova 3

Question 1

What is the function of HPV oncoprotein E6?

Answer 1

E6 binds to tumor suppressor p53 and E6-AP ubiquitin ligase to target p53 for proteosomal degradation

Question 2

What are the 2 functions of HPV oncoprotein E7?

Answer 2

• E7 binds to tumor suppressor Rb (retinoblastoma protein) and E3 ubiquitin ligase to target Rb for proteosomal degradation
• E7 also binds to cell cycle inhibitor protein p21, inactivating it and allowing cell cycling

Question 3

What 2 tumor suppressor proteins does HPV need to inactivate to induce S phase and what oncoprotein is involved?

Answer 3

Rb and p21, HPV E7

Question 4

What are the 3 functions of tumor suppressor protein p53?

Answer 4

• activation of DNA repair enzymes
• arrest of cell cycle OR
• induction of apoptosis

Question 5

What is the role of SV40 sTAg?

Answer 5

Inhibits protein phosphatase 2a (Pp2a) which normally blocks cell growth signalling pathways. As a result, there is prolonged activation of cell growth signalling pathways and MAP kinases become active , stimulating transcription of G1 and S phase molecules

Question 6

What SV40 oncoprotein is able to cause cell transformation independently and which one can’t ?

Answer 6

LTAg can cause cell transformation on its own

sTAg contributes to cell transformation but can’t transform on its own

Question 7

What are the 4 mechanisms employed by SV40 to transform cells?

Answer 7

1) Rb inactivation by LTAg resulting in activation of S phase transcriptional activator E2f
2) p53 sequestration by LTAg
3) Hsp70 binding by LTAg
4) Pp2a inactivation by sTAg resulting in prolonged activation of cell growth signalling pathways

Question 8

What are the 4 mechanism employed by HPV to transform cells?

Answer 8

1) Rb targetting for degradation by E7 and a ubiquitin ligase
2) p53 targetting for degradation by E6 and a ubiquitin ligase
3) p21 inactivation by E7
4) Genome integration to stabilize E6 and E7 mRNA

Question 9

Is transformation a rare occurrence with papova virus infections?

Answer 9

Yes

Question 10

What 2 low probability events must occur in order for SV40/HPV to induce cell transformation?

Answer 10

1) Lethal late genes must NOT be expressed (their spontaneous deletion is rare)
2) LT/sT or E6/E7 must be expressed constitutively (always expressed) and transmitted to every cell infected (vDNA integration promotes cancer)

Question 11

Why are the 2 events required for cell transformation by papova viruses so rare?

Answer 11

Because they are not required for the viral life cycle or transmission