The Saccharomyces cerevisiae ubiquitin-proteasome system
Our studies of the yeast ubiquitin-proteasome pathway have uncovered a number of general principles that govern substrate selectivity and proteolysis in this complex system. Much of the work has focused on the destruction of a yeast transcription factor, MAT alpha 2. The alpha 2 protein is polyubiquitinated and rapidly degraded in alpha-haploid cells. One pathway of proteolytic targeting, which depends on two distinct endoplasmic reticulum-localized ubiquitin-conjugating enzymes, recognizes the hydrophobic face of an amphipathic helix in alpha 2. Interestingly, degradation of alpha 2 is blocked in a/alpha-diploid cells by heterodimer formation between the alpha 2 and a1 homeodomain proteins. The data suggest that degradation signals may overlap protein-protein interaction surfaces, allowing a straightforward steric mechanism for regulated degradation. Analysis of alpha 2 degradation led to the identification of both 20S and 26S proteasome subunits, and several key features of proteasome assembly and active-site formation were subsequently uncovered. Finally, it has become clear that protein (poly) ubiquitination is highly dynamic in vivo, and our studies of yeast de-ubiquitinating enzymes illustrate how such enzymes can facilitate the proteolysis of diverse substrates.
Mark Hochstrasser, Phoebe R. Johnson, Cassandra S. Arendt, Alexander Yu. Amerik, Sowmya Swaminathan, Rob Swanson, Shyr-Jiann Li, Jeffrey Laney, Robin Pals-Rylaarsdam, Jonathan Nowak, Pamela L. Connerly, M. Yanagida, K. A. Nasmyth, M. Tyers, R. T. Hunt, and J. Diffley. "The Saccharomyces cerevisiae ubiquitin-proteasome system" Philosophical Transactions of the Royal Society B 354.1389 (1999): 1513-1522. Available at: http://works.bepress.com/rob_swanson/2