Cell Cycle Control

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Principles Module 33

Objectives

  • Identify the major controlling input for each cell cycle checkpoint
  • Discuss the role of cyclin-dependent kinases

Key Points

Regulation

  • certain cell factors promote transition to division
    • some proteins found to vary in level with cell cycle = cyclins
    • genetic mutants found that regulate progression = cdc’s (cell div cycle)
      • many found to encode kinases, interact with cyclins = cdk’s
  • CDK’s
    • cyclin-dependent kinases, partner with cyclins
    • regulated by phosphorylation, in turn phosphorylate targets
      • enzymes required for cellular processes
  • checkpoints
    • G1/S is primary
      • external factors can influence
      • links cell division to growth and nutritional status
      • accumulation of G1 cyclins activate Cdc2 kinase, activates targets
    • G2/M
      • M-phase promoting factors involved in this check
        • Mitotic cyclin + Cdc2 kinase
      • integrity of DNA after replication critical
    • Spindle
      • tension on MT, chromosomes aligned at metaphase plate
        • unclear how mechanical signaling occurs
      • anaphase-promoting complex (APC) result in cohesin breakdown
        • marks securin for degradation, releases inhibition on separase
  • Growth factors
    • proteins with specific cell surface receptors
    • often trigger MAP kinase cascades that lead to G1 cyclin expression
    • not all cells affected by all growth factors
  • p53 is a tumor suppressor
    • monitors DNA integrity, induces repair enzymes or cell death
  • proto-oncogenes: normal genes that cancer-causing when mutated
    • involved in signaling, either receptors or part of transduction

In-class Activities

Describe some features and characteristics of cells deficient in each of the cell cycle checkpoints. For example, what would a cell deficient in G1/S regulation be like? What would it have or lack?

Questions for Practice

  • Which cell cycle checkpoint is most influenced by external factors? Why is this adaptive?
  • Predict the consequences of a mutation in mitotic cyclin OR p53 OR a proto-oncogene.