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The Saccharomyces cerevisiae ubiquitin-proteasome system
Philosophical Transactions of the Royal Society B (1999)
  • Mark Hochstrasser
  • Phoebe R. Johnson
  • Cassandra S. Arendt
  • Alexander Yu. Amerik
  • Sowmya Swaminathan
  • Rob Swanson, Valparaiso University
  • Shyr-Jiann Li
  • Jeffrey Laney
  • Robin Pals-Rylaarsdam
  • Jonathan Nowak
  • Pamela L. Connerly
  • M. Yanagida
  • K. A. Nasmyth
  • M. Tyers
  • R. T. Hunt
  • J. Diffley

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.

  • yeast,
  • ubiquitin,
  • proteasome,
  • proteolysis,
  • mating type
Publication Date
Fall September 29, 1999
Citation Information
Mark Hochstrasser, Phoebe R. Johnson, Cassandra S. Arendt, Alexander Yu. Amerik, et al.. "The Saccharomyces cerevisiae ubiquitin-proteasome system" Philosophical Transactions of the Royal Society B Vol. 354 Iss. 1389 (1999)
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