Tumour Suppressor Genes, Cell Cycle Clock Flashcards
What happens to TSGs for cancer to occur?
Dysregulated inhibition
During what process can the heterozygosity of Rb be lost?
Meiosis
What are some mechanisms for the loss of heterozygosity in Rb?
Gene conversion
Hemizygosity - section of chromosome discarded
Nodisjunction- error in segegration of chromosomes during mitosis
Epigenetic mechanism of TSG inactivation
Promoter methylation
What induces cell proliferation?
Mitogens
What parts in the cell cycle are similar between cancerous and normal cells?
S-M
What parts in the cell cycle are different between cancerous and normal cells?
Cells responsive to extracellular signals during G1 until R and dysregulation at the R point causes many cancers
What drives the cell cycle clock?
CDK-cyclin complexes
Most cyclinsare driven by programmed fluctuations throughout the cell cycle, which cyclin does not?
D Cyclins
What controls the levels of D cyclins?
Mitogens
What tips cells beyond the R point transition?
pRb (Protein of Rb)- Guardian of the Restriction Gate
What 2 cyclins are responsible for phosphorylating pRb and when?
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.
How is pRb disregulated?
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