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.

31 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cotranslational quality control (QC) is the mechanism by which the cell checks the integrity of newly synthesized proteins and mRNAs. In the event of mistakes these molecules are degraded. The Ccr4-Not complex has been proposed to play a role in this process. It contains both deadenylation and ubiquitination activities, thus it may target both aberrant proteins and mRNAs. Deadenylation is the first step in mRNA degradation. In yeast it is performed by the Ccr4 subunit of the Ccr4-Not complex. Another complex subunit, namely Not4, is a RING E3 ligase and it provides the ubiquitination activity of the complex. It was found associated with translating ribosomes. Thus, it has been suggested that Not4 is involved in ribosome-associated ubiquitination and degradation of aberrant peptides. However, several other E3 ligases have been associated with peptide ubiquitination on the ribosome and the relevance of Not4 in this process remains unclear. In this review we summarize the recent data and suggest a role for Not4 in cotranslational protein QC.
    Frontiers in Genetics 05/2014; 5:141. DOI:10.3389/fgene.2014.00141
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligase gp78, known for its role in protein quality control, is critical for unglycosylated PrP ubiquitylation and degradation. Furthermore, C-terminal sequences of PrP protein are crucial for its ubiquitylation and degradation. Our study reveals the first ubiquitin ligase specifically involved in prion protein PrP degradation and PrP sequences crucial for its turnover. Our data may lead to a new avenue to control PrP level and pathogenesis.
    PLoS ONE 04/2014; 9(4):e92290. DOI:10.1371/journal.pone.0092290 · 3.23 Impact Factor
  • Source
    • "Ubiquitination results in the modification of protein function, thereby controlling cellular processes such as cell cycle progression, differentiation, and stress responses [15, 16]. This 8.5 kDa protein is first activated by ubiquitin-activating enzymes (E1) before being transferred to ubiquitin-conjugating enzymes (E2) and ubiquitin protein ligases (E3) [17]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulation of DNA repair can be achieved through ubiquitin-mediated degradation of transiently induced proteins. In Saccharomyces cerevisiae, Rad4 is involved in damage recognition during nucleotide excision repair (NER) and, in conjunction with Rad23, recruits other proteins to the site of damage. We identified a synthetic interaction upon UV exposure between Rad4 and Cdc20, a protein that modulates the activity of the anaphase promoting complex (APC/C), a multisubunit E3 ubiquitin ligase complex. The moderately UV sensitive Δrad4 strain became highly sensitive when cdc20-1 was present, and was rescued by overexpression of CDC20. The double mutant is also deficient in elicting RNR3-lacZ transcription upon exposure to UV irradiation or 4-NQO compared with the Δrad4 single mutant. We demonstrate that the Δrad4/cdc20-1 double mutant is defective in double strand break repair by way of a plasmid end-joining assay, indicating that Rad4 acts to ensure that damaged DNA is repaired via a Cdc20-mediated mechanism. This study is the first to present evidence that Cdc20 may play a role in the degradation of proteins involved in nucleotide excision repair.
    02/2014; 2014:519290. DOI:10.1155/2014/519290
Show more