copyright © 2005 pearson education, inc. publishing as benjamin cummings frequency of cell division...
TRANSCRIPT
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Frequency of Cell Division
• Varies from cell to cell
– Skin cells divide frequently
– Liver cells only when needed
– Nerve & muscle cells do NOT divide
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
What drives the cell cycle?
• The cell cycle is driven by specific molecular signals present in the cytoplasm
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cell cycle control system
• Molecules in the cell trigger and coordinate key events in the cell cycle
• Compared to the control system on an automatic washing machine
• Cell cycle is regulated at certain checkpoints by both internal and external controls
• Checkpoint = critical control point where stop & go ahead signals are given
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Checkpoints
• G1, G2, and M phases
• G1 is the most important “restriction point”
– If the go ahead signal is given the cell usually completes S, G2 and M phases
– If the go ahead signal is NOT given it enters into a nondividing state called G0
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 12.14 Mechanical analogy for the cell cycle control system
Control system
G2 checkpoint
M checkpoint
G1 checkpoint
G1
S
G2M
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 12.15 The G1 checkpoint
G1 checkpoint
G1G1
G0
(a) If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.
(b) If a cell does not receive a go-ahead signal at the G1checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Regulatory molecules of the cell cycle
• Kinases and cyclins
• Proteins kinases give the go ahead signals at the G1 & G2 checkpoints by phosphorylation
• These kinases are always present but in order to be active they must be attached to a cyclin
• Called Cyclin Dependent kinases (Cdks)
• Fluctuation of MPF (M-phase promoting factor)
• Both Cdk and cyclin are needed to get past the G2 checkpoint
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 12.16 Molecular control of the cell cycle at the G2 checkpoint
Accumulated cyclin moleculescombine with recycled Cdk mol-ecules, producing enough molecules of MPF to pass the G2 checkpoint and initiate the events of mitosis.
MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase.
3
During G1, conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled.
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During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G1 phase.
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2
Synthesis of cyclin begins in late S phase and continues through G2. Because cyclin is protected from degradation during this stage, it accumulates.
1
Cdk
CdkG2
checkpoint
CyclinMPF
Cyclin is degraded
DegradedCyclin
G 1
G 2
S
M
G1G1 S G2 G2SM M
MPF activity
Cyclin
Time
(a) Fluctuation of MPF activity and cyclin concentration during the cell cycle
(b) Molecular mechanisms that help regulate the cell cycle
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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Other factors affecting cell division
• Growth factors – a protein that is released by certain cells that stimulate other cells to divide
• Density-dependent inhibition – when it gets too crowded cells will stop dividing because there is not enough nutrients to support more
• Anchorage dependence – cells must be attached to something in order to divide
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Loss of cell cycle control – Cancer cells
• Cancer cells do not respond normally to the body’s control mechanisms
– Do not exhibit density-dependent inhibition
– Do not stop growing when growth factors are depleted
• Why??
– Maybe they don’t need growth factors or make their own, abnormality in the checkpoints are some of the hypothesis
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cancer in the body
• Transformation – converts a normal cell into a cancer cell
• Normally our body recognizes it & destroys it but sometimes they evade destruction, multiply and form a tumor (mass or lump)
• If the cells remain at the original site the mass is said to be benign
• If the cells move & cause organ damage it is said to be malignant
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Malignant tumor cells
• Abnormal in many ways
– Unusual number of chromosomes
– Metabolisms are disabled
– Lose or destroy attachments to neighbor cells
– Secrete signals that cause blood vessels to grow toward them
– Some can travel in blood and lymph to other parts of the body (metastasis)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Treatment of cancer cells
• Localized tumors – radiation (damages DNA in cancer cells more than normal cells)
• Metastatic tumors – chemotherapy is used (drugs that are toxic to actively dividing cells)
– Taxol – freezes the mitotic spindle by preventing microtubule depolymerization which stops actively dividing cells from going past metaphase
– Sickness, hair loss, nausea result from these drugs effects on healthy cells