Control Points in the Mitotic Cell Cycle

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

12. Normal Ras and Oncogenic Ras Normal Ras Oncogenic Ras

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

14. p53 Domain Structure

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

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

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

18. Cell Cycle Checkpoints

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

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

21. Apoptotic Cell Normal Cell

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

23. 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

24. Mitochondrion

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

26. Bax Disruption of Phospholipid bilayer

27. Release of Cytochrome C from Mitochondria Pg. 628

28. Caspase Activation Pg. 627

29. Caspase Cascade Pg. 627

30. 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

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

32. Stem Cell Concept Pluripotent Multipotent

33. M-Phase Cdk Activity

34. Egg Cell and Sperm Cells Pg. 661

35. M-Phase Cdk Activity

36. 8-cell Embryo (pre-compaction)

37. 50 µm Blastocycst Uterus Inner Cell Mass (ICM) Blastocyst Blastocoel Trophoblast

39. Preimplantation Development (~ 7 days)

40. (~ 9 weeks)

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

42. Isolation of ICM Cells

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

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

45. Teratomas Retinal epithelia Neural epithelia Cartilage Bone

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

47. Stem Cell Therapy

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

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

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