Thecell cycleis mainly regulated by two types of proteins:细胞周期蛋白-dependent kinase (CDK)and细胞周期蛋白. CDKs are protein kinases. Protein kinases are enzymes that activate or inactivate other proteins by phosphorylating them. In order to be active, a CDK needs to form a complex with the correct cyclin.

One type of cyclin-CDK complex, MPF (which stands for “mitotic promoting factor” or “maturation promoting factor”), allows the cell to proceed from the G2检查点into mitosis. At the G2检查点, MPF will phosphorylate a variety of proteins, triggeringmitosis.

The vertical line on a graph indicates the concentration of a cycling, the horizontal line indicates the phase of the cell cycle. The phases are separated from each other on a graph by thick, horizontal lines. Concentration of cyclin C, shown in green, starts to increase at the beginning of G1 phase and rises through the S phase, to decrease at the border between S and G2 phase to reach concentration of 0 at the end of mitosis. Concentration of cyclin E, shown in purple, starts to rise in the middle of the G1 phase, reaches its peak at the border between G1 and S phase, and decreases again to reach the value of 0 in the middle of the S phase. Concentration of cyclin A, shown in red, starts to increase at the end of G1 phase and slowly increases through S phase to reach its peak at the beginning of G2 phase, and then it decreases rapidly to reach the value of 0 at the beginning of mitosis. Concentration of cyclin B, shown in blue, starts to increase at the beginning of S phase, slowly rises through S and G2 phase to reach its peak at the border between G2 and mitosis phase, then rapidly decreases at the end of mitosis.

Figure 1. Cyclins and CDKs throughout the cell cycle.

Animal cells have at least four types of cyclins:G1-phase cyclin, G1/S-phase cyclin, S-phase cyclin, and M-phase cyclin.These types of cyclins will form CDK complexes in relation to their name. For example, S-phase cyclin will bind to its specific CDK and form S-CDK. The CDKs are expressed constantly throughout the entire cycle. By contrast, cyclin is being produced and destroyed at various rates in different cell cycle phases. The rise and fall of cyclin determines the fluctuation of the cyclin-CDK complex.

The fluctuating activities of the different cyclin-CDK complexes are of major importance in controlling all of the stages of the cell cycles.

Each cyclin-CDK complex phosphorylates a different set of proteins. S-CDK will catalyze phosphorylation of the protein that initiates DNA replication. M-CDK phosphorylates condensing proteins, which are essential for chromosome condensation, as well as lamin proteins, which are responsible for the nuclear membrane network. M-CDK also stimulates the assembly of the mitotic spindle by phosphorylating protein for the microtubule.

Beside the cyclin-CDK complex, other extracellular signals regulate cell size and cell number. They can be divided into three major classes:

  • Mitogens三:刺激细胞分裂ggering G1/S-CDK.

  • Growth factor: promotes cell growth by triggering protein synthesis and other macromolecules, and prevents their degradation.

  • Survival factor: promotes cell survival by suppressing apoptosis (programmed cell death).

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