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1. Introduction
2. The cell cycle
3. Somatic cell cycles
4. Negative regulation of G1 progression by Cdk
5. The "Rb pathway" in human cancer
6. Two groups of Ink4 proteins
7. Two groups of CIP/KIP proteins
8. Expression of INK4 genes during embryogenesis
9. Expression of Ink4 genes in tissues of young mice
10. Testicular atrophy, fertility in Ink4d-null male mice
11. Ink4c/Ink4d double deficient male mice are sterile
12. Conclusion (1)
13. Role of Cdk inhibitors in the CNS (1)
14. Hypothesis (1)
15. Role of Cdk inhibitors in the CNS (2)
16. Sensory hair cell loss in Ink4d -/- mice, deafness
17. Ink4d and postmitotic state of sensory hair cells
18. Postnatal development in Ink4d, Kip1-null mice
19. Conclusions (2)
20. Role of the Rb pathway in cerebellar development
21. Medulloblastoma
22. Childhood medulloblastoma
23. Cerebellum - little brain
24. Postnatal cerebellar development
25. Cerebellar development in the mouse
26. The SHH/PATCHED signaling pathway
27. Rb-dependent cell cycle exit and differentiation
28. Ink4c expression in the mouse cerebellum
29. p27Kip1 expression in the IGL
30. N-Myc in GNP proliferation
31. Partial rescue in adult cerebellum
32. Hypothesis (2)
33. Mice lacking Ink4c, p53 develop medulloblastoma
34. Ink4c loss increases medulloblastoma
35. p18INK4C and human medulloblastoma
36. p18Ink4C/CDKN2C expression in medulloblastoma
37. Conclusions (3)
38. Phenotype of Ink4d- or Ink4c- deficient mice
39. Acknowledgments

Topics Covered

• Somatic cell cycle
• Rb pathway
• Positive regulation of G1 phase by phosphorylation of the retinoblastoma protein (Rb) by cyclin-dependent kinases (Cdks)
• Negative regulation of G1 by Cdk-inhibitory proteins (CKIs)
• Rb pathway is often disrupted in cancers
• Two families of CKIs, differential expression in embryogenesis and adult mouse tissues
• Loss of p18Ink4c and p19ink4d induces male sterility
• Loss of p19Ink4d induces progressive deafness after birth
• Loss of p19Ink4d and p27Kip1 induces re-entry of differentiated postmitotic neurons in cycle after birth
• Loss of Ink4c and Patched or p53 induces medulloblastoma, a pediatric tumor of the cerebellum
• CKIs are required for exit from and maintenance of cell cycle exit, or quiescence, a reversible state
• Loss of CKIs leads to sterility, deafness and cancers

Links

Series:

• The Cell Division Cycle

Categories:

• Biochemistry
• Cancer
• Cell Biology
• Neuroscience
• Reproduction & Development

Therapeutic Areas:

• Oncology

Talk Citation

Roussel, M. (2009, April 30). Role and regulation of Cdk inhibitors in development and cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 15, 2025, from https://doi.org/10.69645/YRCJ3134.
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Publication History

• Published on April 30, 2009

Financial Disclosures

• Prof. Martine Roussel has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.