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1. Introduction
2. p53 is a tumor suppressor
3. Evidence that p53 is a tumor suppressor
4. Additional evidence that p53 is a tumor suppressor
5. Half of all human cancers carry p53 mutations
6. p53 is a sequence-specific transcription factor
7. Schematic structure of p53 protein
8. Example: the biological activities of p53
9. Effect of temperature-sensitive p53 activation
10. Induction of cell death by activated p53
11. Activated p53 induces apoptosis in leukemic cells
12. p53 is activated by oncogenic stress
13. p53 is activated by various cellular stress types
14. Induction of p53 by DNA damage (cisplatin)
15. How is p53 activated?
16. Some p53 target genes
17. Activity of transcriptional activation-deficient p53
18. Translocation of p53 in response to DNA damage
19. Transcription activity in response to DNA damage
20. Mitochondrially targeted p53
21. Mitochondrially targeted p53 induces apoptosis
22. Transcriptional activation-deficient and wt p53
23. PUMA releases p53 from Bcl-xL
24. Integrated apoptotic activities of p53
25. How is p53 activity restrained in absence of stress
26. MDM2 - a negative regulator of p53
27. Basic facts about MDM2
28. How does MDM2 inactivate p53?
29. MDM2 promotes degradation of p53
30. p53 levels determine its fate
31. p53-MDM2 negative autoregulatory feedback loop
32. Disrupting the p53-MDM2 feedback loop
33. p53 in evolution
34. p53 transcriptional activity in drosophila embryo
35. Effect of dominant negative p53 activity in the fly
36. C.elegans p53 is required for germ cell apoptosis
37. How is the outcome of p53 activation determined
38. p53 activation: growth arrest or cell death?
39. Induction of p21 by p53 can inhibit apoptosis
40. Some p53 target genes are anti-apoptotic
41. p53 mutations lead to different effects on its action
42. Mutant p53 overexpression prevents apoptosis
43. Mutant p53 protects cancer cells from killing
44. Knock-down of mutant p53 restores killing
45. Mutant p53 down-regulates surface CD95 protein
46. Mutant p53 down-regulates the CD95 promoter
47. p53-based cancer therapy
48. p53-MDM2 binding
49. Drugs that disrupt p53-mdm2 binding - Nutlin
50. Nutlin induces p53 activation/ tumor regression
51. PRIMA-1 affects mutant p53
52. PRIMA-1 synergizes with cisplatin
53. Summary

Topics Covered

• p53 as a tumor suppressor
• Regulation of transcription by p53
• Activation of p53 by oncogenic stress
• Transcriptional and non-transcriptional mechanisms for p53- mediated apoptosis
• Regulation of p53 by Mdm2
• Evolutionary conservation of p53 function
• Mutant p53 gain of function
• p53-based cancer therapy

Links

Series:

• Apoptosis

Categories:

• Cancer
• Cell Biology

Therapeutic Areas:

• Immunology & Inflammation
• Oncology

Talk Citation

Publication History

• Published on October 1, 2007

Financial Disclosures

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