Ubiquitination: the proteasome and human disease

Lectures: 1 session / week, 2 hours / session

The proper functioning of cells depends not only on their ability to synthesize active proteins but also on their ability to turn proteins off when they are not needed. Unneeded proteins are usually targeted for degradation, so the cells can reutilize their amino acids in making up new proteins. Post-translational mechanisms have evolved to generate signals that target proteins for degradation. Tagging the proteins to be destroyed by the attachment of special molecules enables special cellular machines, such as the proteasome, to recognize tagged proteins as substrates. Ubiquitin is a small protein that gets appended as such a "label" to target proteins. In this course we will discuss the mechanisms of the ubiquitin- conjugation system and its importance in the correct functioning of eukaryotic cells. We will study how ubiquitination is the key for the global control of many cellular processes. We will learn how defects in the ubiquitination process are involved in a variety of human disorders, including neurodegenerative diseases (such as Alzheimer's, Huntington's, and Parkinson's); how they affect the activation of the immune response (antigen presentation and the inflammatory response), the regulation of the cell cycle and apoptotic pathways (important in cancer and muscular atrophy) and the ability to downregulate signal transduction pathways (involved in hormonal responses), leading to tumorigenesis. We will also see how viruses like HIV, HPV and other infectious agents deceive their cellular hosts by hijacking cellular machinery involved in regulating ubiquitination to promote their own proliferation. We will discuss how our increasing knowledge of how the ubiquitin system works may facilitate the design of new pharmacological agents to battle disease.

This course is pass/fail. Satisfactory attendance, active participation, and completion of two short assignments are required for a passing grade.

The course focuses on the reading and discussion of two research papers per class. At the end of each class, the necessary background to understand the papers for the next session will be provided. Read handouts and papers before class and be ready to discuss the papers in detail.

For a typical weekly session, you will be required to read two primary literature articles. Read handouts and papers before class and be ready to discuss the papers in detail.

There is one written assignment and one oral presentation assignment.

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