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1. Introduction
2. Apoptosis: cell suicide
3. bcl-2 gene overexpressed in follicular lymphoma
4. Cancer genetics reveal the first apoptosis regulator
5. Phenotype of bcl-2 -/- mice
6. Apoptosis in C. elegans is controlled by 4 genes
7. CED-9 inhibits cell death
8. EGL-1 is a BH3-only protein
9. Evolutionarily conserved pathways to cell death
10. How cell death initiates
11. EGL-1 is a BH3-only protein
12. Mammals bear multiple BH3-only proteins
13. Does Bim antagonize Bcl-2?
14. Bcl-2 promotes and Bim antagonizes cell survival
15. A general model
16. Loss of Bim compansates for loss of Bcl-2
17. BH3-only proteins initiate apoptosis
18. BH3-only proteins monitor cellular well-being
19. Distinct but converging pathways to apoptosis
20. Binding surface formed by BH1, BH2, BH3
21. How selective are BH3-only proteins?
22. BH3-only proteins fall into distinct subsets
23. Bad and Noxa co-operate functionally
24. Both subsets must be neutralized for killing
25. How do pro-survival Bcl-2 proteins keep cells alive?
26. Killing by BH3-only proteins require Bax and Bak
27. Bax, Bak: the other class of Bcl-2-related proteins
28. Some BH3-only proteins directly activate Bax/Bak
29. Apoptosis in the absence of putative activators
30. BH3-only proteins activate Bax/Bak indirectly
31. Bak sequestered in healthy cells by Mcl-1, Bcl-xL
32. Both Mcl-1 & Bcl-xL need to be neutralized
33. Bcl-2 has no direct role in controlling Bak
34. How is Bax regulated?
35. Are there other steps required for activation?
36. Some other outstanding questions
37. Do the pro-survival proteins have other functions?
38. Interactions determine cell survival
39. Deregulation of apoptosis causes disease
40. Acknowledgements

Topics Covered

• Apoptosis
• Discovery of Bcl-2
• Cell death in worms
• Evolutionarily conserved pathways to cell death
• How cell death initiates
• BH3-only proteins
• Control of BH3- only proteins
• Promiscuous and selective BH3-only proteins
• Diverse Bcl-2 prosurvival proteins must be neutralized for apoptosis
• Pro-survival Bcl-2 proteins restrain Bax and Bak
• Apoptosis in the absence of "activator" BH3-only proteins
• BH3-only proteins activate Bax and Bak indirectly
• Control of Bak
• Outstanding questions

Links

Series:

• Apoptosis

Categories:

• Cancer
• Cell Biology

Therapeutic Areas:

• Immunology & Inflammation
• Oncology

Talk Citation

Publication History

• Published on October 1, 2007

Financial Disclosures

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