Cyclins and other proteins signal events in the cell cycle
1. Transitions from G1 to S and G2 to M depend on activation of a protein called cyclin-dependent kinase, or Cdk.
2. A kinase is an enzyme that transfers a phosphate from ATP to different protein(s).
This is called phosphorylation.
3. Activated Cdk transfers phosphates from ATP to certain amino acids of proteins that
then move the cell in the direction of cycling.
4. The Cdk effect on the cell cycle is a common mechanism in eukaryotic cells.
• Studies in sea urchin eggs uncovered a protein called the maturation promoting
factor.
• A mutant yeast that lacked Cdk was found, which stalled at the G1–S boundary.
• These two proteins, one from sea urchins and the other from yeast, were similar
in structure and function. Other Cdks have been found in other organisms, including humans.
5. Cyclin is a protein that interacts with Cdk. Cyclin binding of Cdk exposes the active
site of the kinase.
6. The cyclin-Cdk complex acts as a protein kinase that triggers transition from G1 to S.
The cyclin then breaks down and the Cdk becomes inactive. Several different cyclins
exist, which, when bound to Cdk, phosphorylate different target proteins.
• Cyclin D-Cdk4 acts during the middle of G1. This is the restriction point in G1,
beyond which the rest of the cell cycle is inevitable.
• Cyclin E-Cdk2 acts at the boundary of G1 to S to initiate DNA replication.
• Cyclin A-Cdk2 acts during S and also stimulates DNA replication.
• Cyclin B-Cdk1 acts at the G2-to-M boundary, initiating mitosis.
7. Cyclin-Cdk complexes act as checkpoints. When functioning properly, they allow or prevent the passage to the next cell cycle stage, depending on the extra- and intracellular conditions.
• An example is the effect of p21 on the G1-to-S phase transition.
• If DNA is damaged by UV radiation, p21 is synthesized (a protein of 21,000
daltons).
• It binds to the two different types of G1 Cdk molecules, preventing their activation
until damaged DNA is repaired. The p21 is then degraded, allowing the cell
cycle to proceed.
8. Some targets for cyclin-Cdk complexes include proteins that condense chromosomes and others that cause fragmentation of the nuclear envelope.
9. Cyclin-Cdk defects have been found in some cancer cells.
• A breast cancer with too much cyclin D has been found.
• The protein p53, which inhibits activation of Cdk, is found defective in half of all
human cancers.
Growth factors can stimulate cells to divide
1. Cyclin-Cdk complexes provide internal control for cell cycle decisions.2. Cells in multicellular organisms must divide only when appropriate. They must
respond to external signals, controls called growth factors.
3. Some cells respond to growth factors provided by other cells.
• Platelets release platelet-derived growth factor, which diffuses to the surface of
cells to stimulate wound healing.
• Interleukins are released from one type of blood cell to stimulate division of
another type resulting in body immune system defenses.
• The cells of the kidney make erythropoietin, which stimulates bone marrow cells to divide and differentiate into red blood cells.
4. Cancer cells cycle inappropriately because they either make their own growth factors or no longer require them to start cycling.
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