Cells need to hyper-phosphorylate Rb to inactivate it and to advance from G1 phase

Question 1

How do mitogenic signals stimulate hyper-phosphorylation of Rb to pass the R-point?

Answer 1

1. Mitogen signalling activates TFs such as AP-1
2. AP-1 binds to DNA and codes for cyclin D mRNA
3. Cyclin D mRNA is translated to produce cyclin D
4. Cyclin D binds and activates Cdk4/6
5. D-Cdk4/6 phosphorylates Rb, which inactivates Rb, releasing the inhibition of E2F, marking the end of the R-point
6. E2F is now active and induces gene expression of Cyclin E and other cyclins
7. Cyclin E/Cdk2 hyper phosphorylates Rb and completely inactivates it

Question 2

Thus Rb is the … of the R-point. In order to pass the R-point cells need to … Rb and … E2Fs.

Answer 2

Thus Rb is the controller of the R-point. In order to pass the R-point cells need to inactivate Rb and free E2Fs.

Question 3

… inactivates Rb and … in turn is released.

Answer 3

Hyper-phosphorylation inactivates Rb and E2F in turn is released.

Question 4

As such Rb is active when it is … and acts as the enforcer of the R-point.

Answer 4

As such Rb is active when it is hypo-phosphorylated and acts as the enforcer of the R-point.