Cancer and Cell Cycle Regulation

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Cancer and Cell Cycle Regulation
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The Cell Cycle

• The cell cycle has 4 periods, G1, S, G2, and M.
• Quiescent cells, Go, can move into or out of G1
  phase.

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Cell Cycle Checkpoints
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Major Checkpoint Monitoring Molecules

• Cyclins
• Cyclin Dependent Kinases (CDKs)
• p53 - DNA damage
• RB - Retinoblastoma
• APC - Anaphase Promotin Complex

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p53 Anti-tumorigenic

• p53 suppresses cell replication and growth when
  there is DNA damage.
• Impact of less that diploid complement of p53.

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p53 Activity
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p53 Control

• mdm2 reduces the stability of p53 protein.
• p19 arf inactivates mdm2 and allows activation of
  p53

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Outcome of p53 Activation

• Halts cell cycle until repair is completed.
• Launches cell into apoptosis (programmed cell
  death).

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Loss of RB

• Enables continuous DNA synthesis
• Defects in p16, cyclin D, Cdk4 have same result
• Found in melanoma and liposarcoma

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Anaphase Promoting Complex (APC)
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Checkpoint Failire
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Summary Questions

• What are three major checkpoints in the cell
  cycle?
• Name three tumor suppressor genes.