7.11:
Molecular Factors Affecting Cell Division
Cell division, or the mitotic phase of the cell cycle, is controlled by external chemical stimuli, such as growth factors and hormones, and internal factors, such as cell cycle regulators.
The cell cycle is regulated by a combination of proteins called cyclins and cyclin-dependent kinases or Cdks. Concentrations of different cyclins fluctuate with the different cell cycle phases.
As a cell nears the end of the G2 phase, the cyclin B level rises. At high concentrations, cyclin B forms a complex with Cdk1 called the M-phase promoting factor or MPF.
MPF activity is regulated by phosphorylation and dephosphorylation events that determine if the cell undergoes division or not.
Until the end of G2, Wee1 kinase phosphorylates tyrosine residues on MPF and keeps it inactive. This prevents cell cycle entry and halts the cell at the G2/M-phase.
Once Cdc25 dephosphorylates MPF, a Cdk-activating kinase phosphorylates a conserved threonine on MPF and activates it.
Now the cells undergo mitosis and produce two daughter cells.
7.11:
Molecular Factors Affecting Cell Division
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other regulatory proteins. These regulatory molecules either promote the progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation).
The positive regulator molecules include the cyclins and cyclin-dependent kinases (Cdks) that are essential for cell cycle progression. While the Cdks level remains constant, the levels of four cyclins (cyclin D, E, A & B) fluctuate during the different phases of the cell cycle. Upon binding firmly with Cdk, cyclin is phosphorylated for activation. Cyclin D levels rise in the G1 phase, remain high throughout, and decline in the M phase. Cyclin E level peaks at the juncture of the G1-S phase, while Cyclin A is high during S and G2 phases. As the cell approaches the M phase, the Cyclin B level raises and promotes cell division.
The negative regulatory molecules include the retinoblastoma protein (Rb), p53, and p21, which halt the cell cycle. For example, when p53 detects DNA damage, DNA repair enzymes are recruited to correct the damage. If DNA remains unrepaired, p53 initiates apoptosis or cell death and prevents damaged chromosome duplication. The increased p53 level in the cell may also trigger p21 synthesis. The p21 binds to the Cdk/cyclin complex and halts the cycle progression. The accumulation of p53 and p21 prevents the cells from proceeding to the DNA synthesis (the S phase).
This text is partially adapted from Openstax, Anatomy and Physiology 2e, Section 10.3: Control of the Cell Cycle