L43: Cell proliferation - mitotic signals

• What phase can cells enter when they leave the cell cycle?

  Quiescent phase
• What stimulates cells to leave quiescence?

  Growth factors
• Which cells can be stimulated to re-enter the cell cycle?

  Fibroblasts and lymphocytes
• What is required for re-entry into the cell cycle?

  Mitogenic signals
• What is the typical time-scale for mammalian cells to receive a mitogenic signal?

  14-16 hours
• What happens at the restriction point in the cell cycle?

  The cell is committed to the cell cycle
• Why are cancer cells often resistant to therapies?

  They can enter G0 phase
• What percentage of cancers is treated with radiotherapy?

  27%
• Why does radiotherapy not work well on G0 cells?

  They are not actively dividing
• What percentage of cancers is treated with chemotherapy?

  28%
• How do G0 cells respond to chemotherapy?

  They do not replicate their DNA
• What happens if G0-arrested cancerous cells re-enter the cell cycle?

  A tumor may reform
• What initiates mitogenic signals in cells?

  Binding of ligands to receptors
• What is the role of Ras in mitogenic signaling?

  It recruits and activates signaling pathways
• What does MAPK do in the signaling pathway?

  It amplifies the signal
• What are early response genes stimulated by MAPK?

  c-FOS and c-JUN
• What do c-FOS and c-JUN proteins induce?

  Expression of delayed response genes
• What do delayed response genes include?

  G1 cyclins and their partner CDKs
• What is the significance of cyclin-CDK complexes?

  They prepare the cell for the next phase
• What happens when inappropriate growth signals are present?

  Unchecked proliferation occurs
• What can cause mutational activation of receptors?

  Mutations in the trans-membrane domain
• What percentage of breast cancers have a mutation in c-erbB1?

  ~25%
• What happens with mutated Ras in cancers?

  It is permanently activated
• What percentage of cancers have mutated Ras?

  15-30%
• What is the effect of mutated Raf in malignant melanomas?

  It causes unregulated proliferation
• What percentage of malignant melanomas have mutated Raf?

  ~66%
• How do viral oncogenes affect cell proliferation?

  They mimic c-Jun and c-Fos actions
• What is the overall summary of cell proliferation regulation?

  The cell cycle adjusts speed under conditions
• What are the key components of the cell cycle regulation process?

  • Quiescent phase (G0)
  • Growth factors stimulate re-entry
  • Mitogenic signals required for G1 cyclins and CDKs
  • Mutations in signaling pathways can lead to cancer
• What are the consequences of mutations in cell cycle regulators?

  • Unregulated cell proliferation
  • Resistance to therapies
  • Potential tumor formation
  • Viral oncogenes can mimic growth signals
• What is the significance of the restriction point in the cell cycle?

  • The cell commits to the cell cycle
  • It ensures proper progression through G1
  • It is a checkpoint for DNA integrity
• What are the roles of cyclins and CDKs in the cell cycle?

  • Cyclins regulate the cell cycle phases
  • CDKs partner with cyclins to phosphorylate targets
  • They prepare the cell for division
• What happens to the growth rate in the retardation phase?

  The growth rate progressively slows down
• How does the cell cycle respond to prevailing conditions?

  It runs at different rates
• What organism is mentioned in the context of cell cycle regulation?

  Saccharomyces cerevisiae
• What are the phases of the cell cycle in Saccharomyces cerevisiae?

  • Lag phase
  • Exponential phase
  • Retardation phase
  • Stationary phase
• What occurs in the stationary phase of cell growth?

  Cells stop dividing but can re-enter the cycle
• What is a quiescent phase in the cell cycle?

  It is a phase where cells leave the cycle
• In which phase do most non-dividing mammalian cells enter?

  G0 phase
• How long can post-mitotic cells remain in G0 phase?


  Days, weeks, or a lifetime