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Philos Trans R Soc Lond B Biol Sci. Sep 29, 1999; 354(1389): 1513–1522.
PMCID: PMC1692666
The Saccharomyces cerevisiae ubiquitin-proteasome system.
M Hochstrasser, P R Johnson, C S Arendt, Amerik AYu, S Swaminathan, R Swanson, S J Li, J Laney, R Pals-Rylaarsdam, J Nowak, and P L Connerly
Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637, USA. hocl@midway.uchicago.edu
Abstract
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.
Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of
The Royal Society