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What happens to Rb protein in non-proliferating cells?
What is the role of TGFß in the cell cycle?
What happens to G1 cyclin-CDKs prior to the START point?
What is the function of E2F in the cell cycle?
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What is the result of Rb inactivation?
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What is the function of growth factors in the cell cycle?
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What happens to Rb after degradation of mitotic cyclins at the end of mitosis?
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What is the role of cyclin D-CDK4/6 in the cell cycle?
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What happens to the cell after the restriction point?
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What is the result of E2F activation?
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Study Notes
Cyclins and Kinases
- Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes.
- Cyclins were originally named because their concentration varies in a cyclical fashion during the cell cycle.
- A kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation.
Cyclins vs. Kinases
- Certain cyclins are made at certain times during the cell cycle, and their concentration will rise and fall.
- Cyclins are also destroyed after they are no longer needed by the cell.
- CDKs are not destroyed as they are only activated or deactivated.
Kinases Phosphorylate Cell Signal Molecules
- Certain kinases may have two forms (active and inactive).
- Kinases are enzymes (proteins) that phosphorylate certain molecules or other enzymes.
- Most cell cycle signals are phosphorylated by kinases.
Cyclins Activate Kinases
- Most cell cycle kinases are activated by molecules called cyclins.
- A kinase that requires a cyclin for activation is called a cyclin-dependent kinase or Cdk.
- The cyclin attaches to the Cdk, forming a cyclin-Cdk complex.
MPF (Maturation-Promoting Factor)
- MPF is activated at the end of G2 by a phosphatase, which removes an inhibitory phosphate group added earlier.
- MPF is also called the M phase kinase because of its ability to phosphorylate target proteins at a specific point in the cell cycle and thus control their ability to function.
- MPF promotes the entrance into mitosis (the M phase) from the G2 phase by phosphorylating multiple proteins needed during mitosis.
Cyclin Destruction
- Once the CDK phosphorylates certain signals, the cyclin is destroyed.
- In the cell, the concentration of cyclins will rise and fall depending on the phase of the cell cycle.
- When the cyclin is destroyed, the Cdk returns to an inactive form.
Cyclin Types
- Different types of cyclins include:
- Cyclin D: drives the transition G1 → S
- Cyclin E: commits the cell to DNA replication
- Cyclin A: necessary for the initiation of DNA replication
- Cyclin B: promotes the events of Mitosis
Cyclins/CDKs Control the Cell Cycle
- The cell cycle has several external and internal checkpoints, which involve chemical signals that have been phosphorylated by cyclin-CDK complexes.
- G1/S (R point) checkpoint is the primary determining factor for cell division to take place.
- The G2 checkpoint represents the commitment for starting the process of mitosis.
- The M/spindle checkpoint ensures that all the chromosomes are attached to the spindle in preparation of mitosis.
External Signals Affect Cell Division
- External signals, such as growth factors, can affect cell division.
- Mammalian cells need certain nutrients and regulatory proteins to divide.
- Growth factors can turn on the transcription of early response genes, which in turn activate the transcription of delayed-response genes, including G1 cyclin-CDKs.
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Description
Learn about the role of cyclins and kinases in regulating the cell cycle, including the activation of cyclin-dependent kinase enzymes and the process of phosphorylation.
