Readings | Cellular Garbage Disposal: Misfolded Proteins in Normal Biology and Human Disease | Biology

Course readings.
WEEK #	TOPICS	READINGS
1	Introduction and Course Overview See the Lecture Summary	No readings
2	ER Quality Control and Degradation See the Lecture Summary	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 See the Lecture Summary	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 See the Lecture Summary	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 See the Lecture Summary	No readings
6	Biochemical Approaches to Measure Protein Dislocation See the Lecture Summary	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 See the Lecture Summary	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 See the Lecture Summary	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 See the Lecture Summary	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 See the Lecture Summary	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 See the Lecture Summary	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 See the Lecture Summary	No readings
13	ER-associated Degradation in Disease See the Lecture Summary	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.