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1. Introduction
2. The structure of the 26S proteasome
3. Three active sites of the 20S proteasome
4. Proteasome inhibitors
5. PS-341
6. PS-341 in hematological cancers
7. Proteasome inhibitors in multiple myeloma
8. Archaeal and eukaryotic proteasomes
9. ATP-dependent steps in proteasome function
10. The gated channel of the 20S proteasome
11. HbYX motif is critical for ATP-ring binding
12. The role of peptides from PAN’s C-terminus
13. X-ray diffraction of the proteasome
14. X-ray diffraction and cryo-EM
15. Conformational change in α-subunits (before)
16. Conformational change in α-subunits (after)
17. The open and closed conformations review
18. Prions inhibit the proteasome function
19. PrPSC inhibits proteasome function
20. Inhibition assays with agg. β-PrP and PrPSc
21. Non-toxic PrPs do not inhibit 20S proteasomes
22. Ub-conjugates activate the 26S proteasome
23. Poly-Ub-conjugates stimulate gate-opening
24. Only poly-Ub proteins stimulate peptide hydrolysis
25. Ub conjugates stimulate 26S ATPase activity
26. Ub conjugates activate their own degradation
27. Proteasome activity and USP14 inhibitor
28. Inhibition of USP14 enhances tau degradation
29. Animation of the proteasome activity
30. Points to remember
31. Acknowledgements

Topics Covered

• The 26S proteasome
• The 20S proteasome
• Proteasome inhibitors
• PS-341
• Proteasome inhibitors in multiple myeloma
• Structures of the archaeal PAN ATPase-20S complex and the eukaryotic 26S proteasome
• Multiple ATP-dependent steps in proteasome function
• The gating mechanism of the proteasome
• Prions inhibit proteasome function
• Binding of ubiquitin conjugates activate the 26S proteasome by stimulating 20S gate-opening and ATP hydrolysis
• Ubiquitin conjugates activate their own degradation by the 26S Proteasome
• The inhibitor of proteasome-associated deubiquitinating enzyme Usp14, IU1, enhances degradation of tau

Links

Series:

• Protein Homeostasis

Categories:

• Biochemistry
• Cell Biology
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on October 7, 2014

Financial Disclosures

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