Cell growth + division lecture 11

Question 1

Identification of tumour suppressor

Answer 1

1. Fuse 1 tumour cell + 1 non tumour cell
   - But hard to fuse, large parts of chromosome often lost
2. Look at familial traits
   - Childhood cancer, inherit 1 WT + 1 mutant tumour suppressor from parent
   - Aquire 2nd mutation (↑ chance), often gene conversion event
3. Clone genes that revert transformed cells
4. Identify proteins that interact w/ immortalising oncogenes
   - SV40 T antigen

Question 2

pRb

Answer 2

• Mutated, deleted or interaction w/ viral protein
• Associated w/ ↑ subset
• Re-introductino of WT pRb reverts transformed phenotype → returns to growth factor independence
• cyclinE hyperphosph pRB, pass restriction point
• Different genes have different affinities for pRb
• viral oncogenes bind to pRB in pocket + block ability to interact w/ E2F
• Phosph sites can be mutated
• Histone deacetylases recruit E to inhibit transcription
• Comb of Rb + pRB-like proteins, their phosphorylation state + what E2F they associate w/
• Several targets (e2F → division), Suv39H1 senescence, let-2 differentiation