Description: The ubiquitin/proteasome system (UPS) is one of most conserved mechanisms in eukaryotic evolution. The UPS is a proteolytic system that promotes the degradation of regulatory and damaged proteins, and the biochemical mechanism is very well understood. A Nobel Prize was awarded in 2004, just 20 years after the initial discovery of this mechanism. Notwithstanding this award, many aspects of this pathway are poorly understood. This mini-series of lectures will discuss i), the seminal studies that led to our mechanistic understanding of the UPS, ii), topics that continue to be actively investigated iii), the implication of protein turnover in human diseases, and iv) non-proteolytic roles for ubiquitin and ubiquitin-like systems. This course will introduce you to novel experimental approaches, model systems, and a general appreciation for the intersection of the UPS in diverse biological systems.
Structure: Dr. Madura will present all the lectures. Publications (1-2) pertinent to each lecture and a PowerPoint slide deck will be provided. Students should review the studies and paper(s) before each lecture and be prepared to engage in active discussions.
Outcome: Two key concepts will be understood. First, the conjugation of ubiquitin to other proteins typically marks them for degradation. This process is highly conserved, but also remarkably versatile, permitting different biochemical and cellular effects. Second, the protein ubiquitination step is temporally and spatially separated from degradation by the proteasome. By understanding these biochemical events you will be able to appreciate how a limited number of targeting factors can promote the targeted degradation of thousands of proteins with exquisite specificity.
Grading: Attendance at all lectures is mandatory, and participation in discussion is expected. A take-home final exam will be issued during the last lecture period.
- Attendance = 40% (5%/lecture)
- Discussion = 20%
- Exam = 40%
Course Materials: Publications (research papers and review articles).