Question

The retinoblastoma protein, pRB, is a tumor-suppressor protein that controls the G1/S cell-cycle checkpoint. While pRB is present in all phases of the cell cycle, regulation of its activity is important in the progression from G1 phase to S phase. Sort each statement depending on whether it is is true of cells that remain at the G1 checkpoint or of cells that progress from G1 to S phase.1. pRB phosphorylated 2. pRB not phosphorylated 3. pRB bound to E2F 4. pRB not bound to E2F 5. E2F bound to DNA 6. CDK4 bound to Cyclin D1

Answer 1

Answer:

1. pRB phosphorylated: The cell will not remain in G1 phase i.e. it will enter S phase because pRB will be degraded.

2. pRB not phosphorylated: The cell will remain in G1 phase i.e. will not enter S phase because pRB will remain bound to E2F.

3. pRB bound to E2F: The cell will remain in G1 phase i.e. will not enter S phase.

4. pRB not bound to E2F: The cell will not remain in G1 phase i.e. it will enter S phase.

5. E2F bound to DNA: The cell will not remain in G1 phase i.e. it will enter S phase.

6. CDK4 bound to Cyclin D1:  The cell will not remain in G1 phase i.e. it will enter S phase.

Explanation:

Retinoblastoma protein, pRB supresses tumor by regulating cell cycle progression in G1 phase. When a transcription factor known as E2F is bound to pRB the cell remains in G1 phase and did not proceed further to enter S phase. But as soon as pRB becomes phosphorylated, E2F becomes free and causes gene expression of cyclin E and and cyclin A which are required in progression of cell cycle from G1 phase to S phase.

Signaling involved in cell cycle progression from G1 phase to S phase.

When a cell is unstimulated, pRB is bound to E2F but G1 phase specific growth factors induce the expression of cyclin D through Ras-MAP kinase pathway.

Synthesis of cyclin D leads to the activation of CDK-4 which is a serine-threonine kinase. This kinase causes phosphorylation of pRB which results in the degradation of pRB.

Because of degradation of pRB, E2F becomes free and leads to the expression of cyclin E and and cyclin A which are S phase specific cyclins. This is how cell progresses from G1 phase to S phase.

E2F is a transcription factor which causes expression of S phase specific cyclins i.e. cyclin E and and cyclin A. So, E2F bound to DNA will result in cell cycle progression from G1 phase to S phase.