Rb

Question 1

what does Rb stand for?

Answer 1

retinoblastoma protein (Rbp)

Question 2

is Rbp a tumour suppressor or an oncogene?

Answer 2

tumour suppressor

Question 3

what point of the cell cycle is regulated by Rb?

Answer 3

the restriction point

- point in G1 (before S-phase)

Question 4

what does Rb bind to and what happens to allow cell cycle to continue?

Answer 4

Rb binds and represses E2F transcription factor

• Rb recruits histone deacetylases which cause chromosome compaction and repression of transcription in G1 (prevent entry into Sphase)
• Mitogens upregulate expression of cyclin D
• Cyclin D monophosphorylates/ hypophosphorylates Rb
• Rb loses binding to E2F
• this causes transcription of cell cycle genes e.g. cyclin E
• cyclin E hyperphosphorylates Rb
• Rb falls off complex with histone deacytylase
• cell cycle gene transcription can occur - S-phase and mitosis can occur

Question 5

is the control of Rb peturbed in most cancers?

Answer 5

yes

Question 6

what can activate cyclin D?

Answer 6

• Hh
• cytokines (JAK+STAT pathway)
• growth factors (via RTKs)
• growth factors (via Her/Neu2)
• wnts