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Control Points in the Mitotic Cell Cycle

Control Points in the Mitotic Cell Cycle. Control at the G2/M Transition. DNA Replication. Control at the G1/S Transition. Control Points in the Mitotic Cell Cycle. Positive Control by Cyclin/Cdk. Negative Control By p53 (checkpoint). Cyclin Protein Levels Vary

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Control Points in the Mitotic Cell Cycle

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  1. Control Points in the Mitotic Cell Cycle Control at the G2/M Transition DNA Replication Control at the G1/S Transition

  2. Control Points in the Mitotic Cell Cycle Positive Control by Cyclin/Cdk Negative Control By p53 (checkpoint)

  3. Cyclin Protein Levels Vary During the Cell Cycle

  4. Cyclin/Cdk Complexes During the Cell Cycle Expression of M-cyclin Gene Ubiquitin-dependent proteolysis Ubiquitin-dependent proteolysis Expression of S-cyclin Gene

  5. Cyclin/Cdk Phosphorylates Rb Protein (RTK) (Ras-MAP Kinase) Activation of “S-Phase Genes”

  6. Cell Cycle Checkpoints

  7. Control Points in the Mitotic Cell Cycle Positive Control by Cyclin/Cdk Checkpoint by p53

  8. The p53 Cell Cycle Checkpoint or Short Telomeres (ATM Kinase)

  9. The p53 Cell Cycle Checkpoint or Short Telomeres DNA Repair System (ATM Kinase) Programmed Cell Death

  10. Connection to Cancer RTK/Ras pathway HER2 gene amplifications Ras Checkpoint pathway p53 ATM Kinase

  11. Normal Ras and Oncogenic Ras Normal Ras Oncogenic Ras

  12. Connection to Cancer RTK/Ras pathway HER2 gene amplifications Ras Checkpoint pathway p53 ATM Kinase

  13. p53 Domain Structure

  14. Cyclin/Cdk Complexes During the Cell Cycle Expression of M-cyclin Gene Ubiquitin-dependent proteolysis Ubiquitin-dependent proteolysis Expression of S-cyclin Gene

  15. Cyclin/Cdk Phosphorylates Nuclear Lamins M-Cyclin/Cdk

  16. P Cyclin/Cdk Phosphorylates APC M-Cyclin/Cdk

  17. Cell Cycle Checkpoints

  18. Cyclin/Cdk Complexes During the Cell Cycle Expression of M-cyclin Gene Ubiquitin-dependent proteolysis Ubiquitin-dependent proteolysis Expression of S-cyclin Gene

  19. Necrosis and Apoptosis Loss of Homeostasis Membrane rupture Release of cellular contents (no inflammation)

  20. Apoptotic Cell Normal Cell

  21. Apoptosis (Programmed Cell Death) Regulated Response to: Extra-cellular “death” signaling molecules DNA Damage

  22. Apoptosis (Programmed Cell Death) ~ 50% of nerve cells are eliminated by apoptosis during development Sculpting of digits “Self-reactive” T- cells are eliminated by apoptosis Protect organism from mutations Aging

  23. Mitochondrion

  24. Apoptotic Receptors and Signal Molecules “Death” Signaling Molecules “Death” Receptor TNF FasL TRAIL

  25. Bax Disruption of Phospholipid bilayer

  26. Release of Cytochrome C from Mitochondria Pg. 628

  27. Caspase Activation Pg. 627

  28. Caspase Cascade Pg. 627

  29. Apoptosis -- Links to Disease Many types of cancer cells are “apoptosis resistant” Apoptosis resistance in autoimmune diseases Overactive neuronal apoptosis in Alzheimer’s and Parkinson’s Thalidomide induces apoptosis

  30. Stem Cell Concept Signal Molecules Signal Molecules Commitment and Differentiation Pg. 721

  31. Stem Cell Concept Pluripotent Multipotent

  32. M-Phase Cdk Activity

  33. Egg Cell and Sperm Cells Pg. 661

  34. M-Phase Cdk Activity

  35. 8-cell Embryo (pre-compaction)

  36. 50 µm Blastocycst Uterus Inner Cell Mass (ICM) Blastocyst Blastocoel Trophoblast

  37. Preimplantation Development (~ 7 days)

  38. (~ 9 weeks)

  39. Sperm cells In Vitro Fertilization (IVF) Embryos (4-cell stage)

  40. Isolation of ICM Cells

  41. Pluripotent Embryonic Stem Cells Signal A Signal B Signal C IVF “Stem Cell Line” Signal D Signal E Pg. 724

  42. Colony of Human Embryonic Stem Cells Stem Cells Mouse “feeder” cells

  43. Teratomas Retinal epithelia Neural epithelia Cartilage Bone

  44. Pluripotent Embryonic Stem Cells Signal A Signal B Signal C IVF “Stem Cell Line” Signal D Signal E Pg. 724

  45. Stem Cell Therapy

  46. “Donor” Somatic Cell Nuclear Transfer Reconstructed Zygote “enucleated egg” Pg. 725

  47. Science 318: 1917-1920 December 21, 2007

  48. Nature 456: 344-349 November 20, 2008

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