Regulation of Cell Division

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Regulation of Cell Division
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Coordination of Cell Division
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Frequency of Cell Division

• Varies with Cell Type

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Cyclin

• Proteins
• Rises and Falls with cell cycle
• Regulate the timing of the cell cycle
• Function by binding to kinases
• Kinases ? transfer a phosphate
• group from ATP to other enzymes to
• activate them

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Example in G2

• Mitotic Cyclins accumulate ? stimulate kinases
• Kinases activate breakdown of nuclear envelope,
  condensation of chromosomes
• More cyclin accumulates ? other kinases activate
  spindle formation.
• Another ex
• Enzymes to breakdown protein attaching sister
  chromatids

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Checkpoint Control System

• Monitors DNA, chromosomes, mitotic spindle
• Proteins that detect mistakes and halt cycle
• Cell cycle arrest

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G1 Checkpoint

• G1 cyclins most important
• Accumulate in late G1
• Peak during S phase
• Restriction point
• Go signal divides
• Stop signal G0

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G2 Checkpoint Mitotic Checkpoint

• G2
• DNA synthesis completed properly?
• Commitment to mitosis
• Mitotic
• Spindle checkpoint
• Can sister chromatids separate correctly?

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Example p53

• Detects mismatched DNA pairs
• Activates cell cycle inhibitors
• Prevent G1 Cyclin kinase from bringing cell into
  S phase
• Damage repaired p53 then inactivated

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Regulators

• Two types of regulatory proteins
• Internal Regulators
• Prevents cells from entering mitosis
• until all chromosomes replicated
• Prevents cell from entering anaphase until all
  its chromosomes are attached to the mitotic
  spindle
• External Regulators
• Proteins respond to events outside of cell
• Direct cell to speed up or slow down cell
  division
• Growth Factors embryonic development wounds
• Molecules on cell surfaces Slow down or stop

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External Signals

• Growth Factors
• External signals
• Protein signals released by body cells
• stimulating division
• Density dependent inhibition
• crowded cells stop dividing
• mass of cells use up growth factors
• Anchorage dependence
• to divide cells must be attached to substrate

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Growth Factor Signals
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Example of a Growth Factor
Platelet Derived Growth Factor (PDGF) made by
platelets (blood cells) binding of PDGF to
cell receptors stimulates connective tissue
cell division (wound repair)
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Growth Factors and Cancer

• Proto-oncogenes
• Normal genes become cancer causing when mutated
• Stimulate cell growth
• Oncogenes stimulate cell to leave G0 and divide
  with or without a signal from outside
• Tumor Suppressor Genes
• Inhibits cell division
• If switched off can cause cancer
• Example p53 in G1

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Development of Cancer
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What causes these hits?

• Mutations in cells can be caused by
• UV radiation Pollution
• Chemical exposure Genetics
• Radiation exposure Age
• Heat Cigarette Smoke

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Tumors

• Mass of abnormal cells
• Benign Tumor
• Abnormal cells remain at original site as a lump
• P53 has halted cell division
• Most do not cause serious problems and removed by
  surgery
• Malignant Tumor
• Cells leave original site
• Lose attachment to nearby cells
• Carried by blood and lymph system to other
  tissues
• Start more tumors metastasis

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Traditional Treatments for Cancer

• Target rapidly dividing cells
• High energy radiation chemotherapy with toxic
  drugs

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New Miracle Drugs

• Drugs targeting proteins (enzymes) found only in
  tumor cells
• Gleevec
• Treatment for adult leukemia and stomach cancer