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1. Introduction
2. The cell cycle
3. Crystal structure of Cdk2 bound to cyclin A
4. Periodicity in cyclin expression
5. Regulation of Cdks
6. Focusing on Cdk2
7. Cdk2
8. Cdk2-/- knockout mice
9. Cdk2-/- knockout mice are viable
10. Atrophy in testis of Cdk2-/- mice
11. Absence of oocyte development in Cdk2-/- mice
12. Expression of cell cycle regulators
13. Kinase activity and Cdk/cyclin complexes
14. Growth defect in Cdk2-/- MEFs
15. Cdk complexes and activity in MEFs
16. Cdk2-/- MEF analysis after starvation
17. Cdk activity in synchronized MEFs
18. Delayed immortalization in Cdk2-/- MEFs
19. Summary Cdk2
20. Is there another gene that compensates for Cdk2?
21. The Retinoblastoma (Rb) protein pathway
22. Cdk2-/-Cdk4-/- double knockout mice
23. Double mutants die around E15
24. Heart defects in Cdk2-/-Cdk4-/- embryos
25. In vivo proliferation in Cdk2-/-Cdk4-/- embryos
26. Hypophosphorylated Rb
27. Impaired proliferation in Cdk2-/-Cdk4-/- MEFs
28. S phase entry defect in Cdk2-/-Cdk4-/- MEFs
29. Rb phosphorylation in Cdk2-/-Cdk4-/- MEFs
30. Rb defect in Cdk2-/-Cdk4-/- MEFs
31. Senescence in Cdk2-/-Cdk4-/- MEFs
32. HPV-E7
33. HPV-E7 mutants
34. Effect of Cdk2-/-Cdk4-/- on Cdk1 expression
35. Summary Cdk2-/-Cdk4-/-
36. What is going on in the S phase?
37. The p27 network
38. Cdk2-/-p27-/- double knockout mice
39. Cdk2-/- and p27-/- mice vs. WT
40. Cdk2-/-p27-/- mice
41. Ovary tumors in Cdk2-/-p27-/- mice
42. Pituitary tumors
43. Normal levels of cell death in the thymus
44. High levels of S phase and mitosis in thymus
45. Cdk activity in the absence of Cdk2 and p27
46. Cdk1 binds to p27 and cyclin E
47. Proliferation of MEFs
48. Silencing of Cdk1 in Cdk2-/- MEFs
49. Summary Cdk2-/-p27-/-
50. Cdk1/cyclin E complexes can drive S phase
51. Cdk1 compensates for Cdk2
52. Premature translocation to the nucleus of Cdk1
53. DNA damage response in Cdk2-/- knockout mice
54. Response to gamma-irradiation in MEFs (1)
55. Response to gamma-irradiation in MEFs (2)
56. Partial hepatectomy model for in vivo response
57. Molecular outcome of gamma-irradiation
58. Co-localization of Cdk1 and p21
59. Proliferation of MEFs after irradiation
60. Cdk2-/- mice are sensitive to gamma-irradiation
61. DNA damage: comet assay
62. DNA damage: gamma-H2AX staining
63. Disturbed kinetics of DNA damage foci
64. DNA damage pathway
65. DNA damage in the absence of Cdk2
66. Acknowledgments

Topics Covered

• Cell cycle regulation during mouse development and adulthood
• Cyclin-dependent kinases (Cdks)
• The genetic pathways for cell cycle regulation
• Cdk1, Cdk2, Cdk4, and Cdk6
• The in vivo functions of Cdk2
• Compensation between different Cdk/cyclin complexes
• Genetic interaction between Cdk2 and Cdk4
• Control of the G1/S phase transition by the Retinoblastoma protein (Rb)
• DNA damage response in the absence of Cdk2
• p27Kip1 inhibits Cdk1 in vivo
• Cdk1/cyclin E complexes promote S phase
• Cdks and tumors

Update Available

The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.

1. Embed full lecture Full lecture Duration: 61:43 min Embed full lecture
2. Embed Update Interview Update Interview Duration: 11:32 min Embed Update Interview

Links

Series:

• The Cell Division Cycle

Categories:

• Cancer
• Cell Biology

Therapeutic Areas:

• Oncology

Talk Citation

Publication History

• Published on April 30, 2009
• Updated on May 28, 2020

Financial Disclosures

• Dr. Philipp Kaldis has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.