The Ubiquitin-Proteasome System of Saccharomyces cerevisiae

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Genetics (Impact Factor: 5.96). 10/2012; 192(2):319-60. DOI: 10.1534/genetics.112.140467
Source: PubMed


Protein modifications provide cells with exquisite temporal and spatial control of protein function. Ubiquitin is among the most important modifiers, serving both to target hundreds of proteins for rapid degradation by the proteasome, and as a dynamic signaling agent that regulates the function of covalently bound proteins. The diverse effects of ubiquitylation reflect the assembly of structurally distinct ubiquitin chains on target proteins. The resulting ubiquitin code is interpreted by an extensive family of ubiquitin receptors. Here we review the components of this regulatory network and its effects throughout the cell.

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    • "The CP provides the proteolytic function of the proteasome and comprises a stack of four seven-membered rings; the outer rings contain 7 distinct α subunits (α1–α7) and the inner rings contain 7 distinct β subunits (β1–β7), three of which possess catalytic activity in eukaryotes (Groll et al., 1997; Unno et al., 2002). The UPS is responsible for the degradation of the majority of intracellular proteins in eukaryotes (Finley et al., 2012) and UPS function impacts virtually every cellular process, from the cell cycle, to DNA replication, to apoptosis, to differentiation , etc. Since exposure to cadmium can affect normal copper homeostasis (Heo et al., 2010), we reasoned that proteasome mutants may exhibit altered response to copper as well. This would be relevant to increasing our understanding of the role of the UPS in copper metabolism (Ooi et al., 1996; Bertinato and L'Abbe, 2003; Burstein et al., 2004; Liu et al., 2007; Brady et al., 2010). "
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    • "Defective mRNA fragments are first deadenylated at the 3′ and decapped at the 5′ end of the molecule, before being degraded by the corresponding exonucleases. Defective polypeptides produced as a result of ribosome stalling are recognized and degraded by the ubiquitin–proteasome system (UPS; Ciechanover, 1998; Goldberg, 2003; Finley et al., 2012). The UPS involves the proteasome, a highly conserved large multicatalytic protease that degrades misfolded proteins or proteins whose presence in the cell is no longer needed. "
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    • "Ubiquitin (Ub) is an abundant small protein best known as a molecular flag that marks proteins for destruction by the 26S proteasome in eukaryotes [1], [2]. The key specificity factors in Ub-mediated proteasomal proteolysis are Ub-protein ligases (E3s), which recognize substrates and attach chains of Ub molecules onto them with the help of several other enzymes (i.e., E1 and E2) [1], [2]. "
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