1. Cell-Cycle Control and Cell Death
Chapter 18
Cell-Cycle Control and Cell Death

2. 1. Overview of the Cell Cycle
Events of eucaryotic cell division

3. Phase of the cell cycle

4. 1) The cell cycle control system can be dissected genetically in yeasts
Comparison of the cell cycle of fission yeasts and budding yeasts

5. Behavior of a temp.-sensitive cdc mutant
Morphology of budding yeast cells arrested by a cdc mutation

6. 2) Analyzing methods for cell-cycle control system
(1) Usage of animal embryo
Oocyte growth and egg cleavage in Xenopus

7. In a cell-free system

8. (2) Studies in culture

9. (3) Cell-cycle progression analysis
Labeling the specific phase of cell cycle
Analysis of DNA content with a flow cytometer

10. 1) Control system can arrest the cell cycle at specific checkpoint
2. Components of cell-cycle control system
1) Control system can arrest the cell cycle at specific checkpoint

11. 2) Cell-cycle control system is based on cyclically activated protein kinases
(1) Core of the cell-cycle control system

13. (2) Structural basis of cdk activation

14. (3) Cdk activity can be suppressed both by inhibitory phosphorylation and by inhibitory proteins
Regulation of cdk activity by inhibitory phosphorylation
Inhibition of a cyclin-cdk complex by a CKI

15. 3) The cell-cycle control system depends on cyclical proteolysis

17. 3. Intracellular control of cell-cycle events

18. 1) S-phase cyclin-Cdk complex (S-Cdks) initiate DNA replication once per cycle

19. 2) Cohesins help hold sister chromatids together

20. 3) Activation of M-phase cyclin-Cdk complex (M-Cdks) trigger entry into mitosis

21. 4) Checkpoint for chromosome separation
(1)Entry into mitosis is blocked by incomplete DNA replication: the DNA replication checkpoint
(2) M-Cdk prepares the duplicated chromosomes for separation

22. (3) Sister chromatid separation is triggered by proteolysis

23. (4) Unattached chromosomes block sister-chromatid separation: The spindle-attachment checkpoint
Mad2 protein on unattached kinetochores

24. 5) G1 phase is a state of stable Cdk inactivity
The creation of a G1 phase by stable Cdk inhibition after mitosis

25. 6) Rb protein acts as a brake in mammalian G1 cells
Mechanisms controlling S-phase initiation in animal cells

26. 7) Cell-cycle progression is blocked by DNA damage and p53” DNA damage checkpoint

27. 4. Programmed cell death (apoptosis)

28. 1) Apoptosis kills cells quickly and cleanly

29. 2)Apoptosis is mediated by an intracellular proteolytic cascade
Procaspase activation
DNA ladder

30. Fas-mediated apoptosis

31. Release of cytochrome c from mitochondria during apoptosis
3) The intrinsic pathway of apoptosis depends on mito.
Release of cytochrome c from mitochondria during apoptosis

32. Intrinsic pathway of apoptosis

33. Role of BH123 pro-apoptotic Bcl2 proteins(Bax & Bak)
4) Bcl-2 protein regulate the intrinsic pathway of apoptosis
3 classes of Bcl2 proteins
Role of BH123 pro-apoptotic Bcl2 proteins(Bax & Bak)

34. How pro-apoptotic BH3-only and anti-apoptotic bcl2 proteins regulate the intrinsic pathway of apoptosis?

35. 5) IAPs inhibit caspases
Model for the roles of IAPS & anti-IAPs in the control of apoptosis in mammalian cells

36. 5. Extracellular control of cell division, cell growth, and apoptosis
Mitogens (Ex. PDGF, TGFβ)
(1) stimulate cell division
platelet

37. (2) Mitogens stimulates G1-cdk and G1/S-Cdk activities

38. 2) Abnormal proliferation signals cause cell-cycle arrest or cell death

39. 3) Extracellular growth factor stimulate cell growth

40. 4) Survival factors allow animal cells to avoid apoptosis
(1) Cell death helps match the number of developing nerve cells to the number of target cells they contact

41. (2) Survival factors often suppress apoptosis by regulation Bcl-2 family members

42. 5) Proliferating cells usually coordinate their growth & division
Potential mechanisms for coordinating cell growth & division

43. Ex. Myostatin deficient

44. Section of kidney tubules from salamander larvae of different ploidies