III. Signal transduction and cell cycle | 50. Regulation of the cell cycle in the G2 and M phases

Question 1

I. MAIN STEPS OF THE CELL CYCLE AND THEIR REGULATION
1. What are the main steps of the cell cycle and their regulation?

Answer 1

1. Growth factor (mitogen) binds to its receptor
2. Signaling pathways are set into motion (MAP kinase cascade)
3. G1 cyclins and Cdks get induced, the cell grows
4. G1 Cdk-cyclin complexes reach a critical point, where they overcome CKIs (restriction point). They lead to induction of proteins needed for replication and of S cyclins
5. G1 Cdks deactivate an S phase CKI, thus SPF (S-phase promoting factor) is released from inhibition (the phosphorylated CKI gets ubiquitinated and degraded)
6. SPF activates pre-replication complexes (already attached to DNA)
7. DNA starts doubling
8. MPF (M-phase promoting factor) remains inactive until the completion of replication and cell growth
9. Once DNA has been entirely doubled and cell size is appropriate at the end of G2 phase, MPF will be activated
10. MPF conducts mitosis until anaphase
11. APC takes control, and the cell divides in two

Question 2

II. Main steps in the regulation of cell cycle in the G2 and M phases
2. What are the steps of the cell cycle in G2 and M phases?

Answer 2

8/ MPF (M-phase promoting factor) remains inactive until the completion of replication and cell growth
9/ Once DNA has been entirely doubled and cell size is appropriate at the end of G2 phase, MPF will be activated
10/ MPF conducts mitosis until anaphase
11/ APC takes control, and the cell divides in two

Question 3

II. Main steps in the regulation of cell cycle in the G2 and M phases
2. In cell cycle, what happen during step 8?

Answer 3

8. MPF (M-phase promoting factor) remains inactive until the completion of replication and cell growth
   - During G2, the increase in cyclin B (cyclins of the G2/M phase) will lead to a corresponding accumulation of Cdk1 (Cdk of the G2/ M phase)
   -> Cdk (1)-cyclin B complex = MPF
   - Cdk in these complexes is phosphorylated at an activating site by CAK (Cdk-activating kinase)
   - Simultaneously, protein kinase Wee1 holds it in an inactive state by inhibitory phosphorylation of tyrosine + threonine residues

Question 4

II. Main steps in the regulation of cell cycle in the G2 and M phases
3. In cell cycle, what happen during step 9?

Answer 4

Step 9: Once DNA has been entirely doubled and cell size is appropriate at the end of G2 phase, MPF will be activated
- The phosphate Cdc25 will dephosphorylate Cdk
-> removing the inhibitory phosphates
-> active MPF
-> triggers mitosis
- Active MPF will have positive feedback effect: stimulation of Cdc25 + suppression of Wee1

Question 5

II. Main steps in the regulation of cell cycle in the G2 and M phases
4. In cell cycle, what happen during step 10?

Answer 5

Step 10; MPF conducts mitosis until anaphase
- APC (anaphase promoting complex) will get activated
- APC will cause the degradation of MPF and the continuation of the cell-cycle in anaphase

Question 6

II. Main steps in the regulation of cell cycle in the G2 and M phases
5. In cell cycle, what happen during step 11?

Answer 6

Step 11: APC takes control, and the cell divides in two
- APC will initiate the process of the separation of the sister-chromatids cohesion
- APC will target the inhibitory protein securin for destruction (by ubiquitin ligase)
- Securin usually binds and
inhibits a protease called separase, but the destruction of securin will release separase
- Separase will now cleave the cohesin proteins between the sister chromatids, separating them

Question 7

III. Roles of Cdk-cyclin complexes in the cell cycle
1. Fill in the table

Answer 7

1. Cdk4,6
2. Cdk2
3. Cdk2
4. Cdk1
5. Cdk7

Question 8

III. Roles of Cdk-cyclin complexes in the cycle
2. Fill the name of cyclin in the table

Answer 8

1. Cyclin D
2. Cyclin E
3. Cyclin A
4. Cyclin B
5. Cyclin H

Question 9

III. Roles of Cdk-cyclin complexes in the cycle
3. Fill in square 1

Answer 9

Question 10

III. Roles of Cdk-cyclin complexes in the cycle
5. Fill in square 3

Answer 10

• SPF: start and maintain DNA replication
• Phosphorylation of certain components of the pre-replication complex

Question 11

III. Roles of Cdk-cyclin complexes in the cycle
6. Fill in square 4

Answer 11

• MPF: conduct mitosis until metaphase
• Phosphorylation of condensin, histones, lamins, micro tubular proteins and GM130
• Finally activation of APC

Question 12

III. Roles of Cdk-cyclin complexes in the cycle
7. Fill in square 5

Answer 12

CAK: general Cdk activating kinase