WEEK # | TOPICS | READINGS |
---|---|---|
1 |
Introduction and Course Overview | No readings |
2 |
ER Quality Control and Degradation |
Werner, E. D., J. L. Brodsky, et al. "Proteasome-Dependent Endoplasmic Reticulum Associated Protein Degradation: An Unconventional Route to a Familiar Fate." Proc Natl Acad Sci USA 93 (1996): 13797–801. (PDF) Jarosch, E., C. Taxis, et al. "Protein Dislocation from the ER Requires Polyubiquitination and the AAA-ATPase Cdc48." Nature Cell Biology 4 (2002): 134–9. |
3 |
Discovery of Ubiquitin as a Tag for Proteasomal Degradation |
Ciechanover, A., S. Elias, et al. "Characterization of the Heat-Stable Polypeptide of the ATP-Dependent Proteolytic System from Reticulocytes." Journal of Biological Chemistry 255, no. 16 (1980): 7525–8. (PDF - 1.4MB) Wilkinson, K. D., M. K. Urban, et al. "Ubiquitin is the ATP-Dependent Proteolysis Factor I of Rabbit Reticulocytes". Journal of Biological Chemistry 255, no. 16 (1980): 7529–32. (PDF) |
4 |
The Ubiquitin Conjugation Cascade |
Finley, D., A. Ciechanover, et al. "Thermolability of Ubiquitin-activating Enzyme from the Mammalian Cell Cycle Mutant ts85." Cell 37, no. 1 (1984): 43–55. Ciechanover, A., D. Finley, et al. "Ubiquitin Dependence of Selective Protein Degradation Demonstrated in the Mammalian Cell Cycle Mutant ts85." Cell 37, no. 1 (1984): 57–66. |
5 |
Biology Seminar | No readings |
6 |
Biochemical Approaches to Measure Protein Dislocation |
Wahlman, J., G. N. DeMartino, et al. "Real-Time Fluorescence Detection of ERAD Substrate Retrotranslocation in a Mammalian in Vitro System." Cell 129, no. 5 (2007): 943–55. Ikeda, Y., G. N. Demartino, et al. "Regulated Endoplasmic Reticulum-Associated Degradation of a Polytopic Protein: P97 Recruits Proteasomes to Insig-1 before Extraction from Membranes." Journal of Biological Chemistry 284, no. 50 (2009): 34889–900. (PDF - 2.9MB) |
7 |
The Putative Dislocon: Lessons from Yeast and Mammalian Systems |
Lilley, B., and H. Ploegh. "A Membrane Protein Required for Dislocation of Misfolded Proteins from the ER." Nature 429, no. 24 (2004): 834–40. Ye, Y., Y. Shibata, et al. "A Membrane Protein Complex Mediates Retro-Translocation from the ER Lumen into the Cytosol." Nature 429, no. 24 (2004): 841–7. |
8 |
Substrate Recognition: The Glycan Destruction Signal for ERAD |
Hammond C., I. Braakman, et al. "Role of N-Linked Oligosaccharide Recognition, Glucose Trimming and Calnexin in Glycoprotein Folding and Quality Control." Proc Natl Acad Sci USA 91, no. 3 (1994): 913–7. Quan, E. M., Y. Kamiya, et al. "Defining the Glycan Destruction Signal for Endoplasmic Reticulum-Associated Degradation." Molecular Cell 32, no. 6 (2008): 870–7. |
9 |
Cytosolic Regulation of Misfolded/Mislocalized Protein Degradation |
Hessa, T., A. Sharma, et al. "Protein Targeting and Degradation are Coupled for Elimination of Mislocalized Proteins." Nature 475, no. 7356 (2011): 394–7. Wang, Q., Y. Liu, et al. "A Ubiquitin Ligase-Associated Chaperone Holdase maintains Polypeptides in Soluble States for Proteasome Degradation." Molecular Cell 42, no. 6 (2011): 758–70. |
10 |
Viral Avoidance and Exploitation of the Ubiquitin Proteasome System |
Barel, M. T., G. C. Hassink, et al. "Human Cytomegalovirus-Encoded US2 and US11 Target Unassembled MHC Class I Heavy Chains for Degradation." Molecular Immunology 43, no. 8 (2006): 1258–66. Wiertz, E. J., T. R. Jones, et al. "The Human Cytomegalovirus US11 Gene Product Dislocates MHC Class I Heavy Chains from the Endoplasmic Reticulum to the Cytosol." Cell 84, no. 5 (1996): 769–79. |
11 |
Toxin Invasion through the ERAD Machinery |
Tsai, B., C. Rodighiero, et al. "Protein Disulfide Isomerase Acts as a Redox-Dependent Chaperone to Unfold Cholera Toxin." Cell 104, no. 6 (2001): 937–48. Bernardi, K. M., J. M. Williams, et al. "The E3 Ubiquitin Ligases Hrd1 and gp78 Bind to and Promote Cholera Toxin Retro-Translocation." Molecular Biology Cell 21, no. 1 (2010): 140–51. (PDF - 3.3MB) |
12 |
Student Oral Presentations | No readings |
13 |
ER-associated Degradation in Disease | Jensen, T. J., M. A. Loo, et al. "Multiple Proteolytic Systems, Including the Proteasome, Contribute to CFTR Processing." Cell 83, no. 1 (1995): 129–35. |