Tumour Suppressor Genes, Cell Cycle Clock

Question 1

What happens to TSGs for cancer to occur?

Answer 1

Dysregulated inhibition

Question 2

During what process can the heterozygosity of Rb be lost?

Answer 2

Meiosis

Question 3

What are some mechanisms for the loss of heterozygosity in Rb?

Answer 3

Gene conversion
Hemizygosity - section of chromosome discarded
Nodisjunction- error in segegration of chromosomes during mitosis

Question 4

Epigenetic mechanism of TSG inactivation

Answer 4

Promoter methylation

Question 5

What induces cell proliferation?

Answer 5

Mitogens

Question 6

What parts in the cell cycle are similar between cancerous and normal cells?

Answer 6

S-M

Question 7

What parts in the cell cycle are different between cancerous and normal cells?

Answer 7

Cells responsive to extracellular signals during G1 until R and dysregulation at the R point causes many cancers

Question 8

What drives the cell cycle clock?

Answer 8

CDK-cyclin complexes

Question 9

Most cyclinsare driven by programmed fluctuations throughout the cell cycle, which cyclin does not?

Answer 9

D Cyclins

Question 10

What controls the levels of D cyclins?

Answer 10

Mitogens

Question 11

What tips cells beyond the R point transition?

Answer 11

pRb (Protein of Rb)- Guardian of the Restriction Gate

Question 12

What 2 cyclins are responsible for phosphorylating pRb and when?

Answer 12

D Cyclin-CDK4/6 complexes phosphorylates the protein to do the hypophosphorylated state.
E Cyclin rises during the R point and E Cyclin-CDK2 phosphorylates the protein to the hyperphosphorylated state.

Question 13

How is pRb disregulated?

Answer 13

Mutation of Rb
Methylation of the Rb promoter
Inactivation by viral oncoproteins
Excessive accumulation of cyclin D1
Inhibition of pRb phosphorylation at M/G1 transition by PP1 phosphotase
Inhibition of CKIs