Protein Quality Control of the Endoplasmic Reticulum and Ubiquitin-Proteasome-Triggered Degradation of Aberrant Proteins: Yeast Pioneers the Path

Annu Rev Biochem. 2018 Jun 20;87:751-782. doi: 10.1146/annurev-biochem-062917-012749. Epub 2018 Feb 2.

Abstract

Cells must constantly monitor the integrity of their macromolecular constituents. Proteins are the most versatile class of macromolecules but are sensitive to structural alterations. Misfolded or otherwise aberrant protein structures lead to dysfunction and finally aggregation. Their presence is linked to aging and a plethora of severe human diseases. Thus, misfolded proteins have to be rapidly eliminated. Secretory proteins constitute more than one-third of the eukaryotic proteome. They are imported into the endoplasmic reticulum (ER), where they are folded and modified. A highly elaborated machinery controls their folding, recognizes aberrant folding states, and retrotranslocates permanently misfolded proteins from the ER back to the cytosol. In the cytosol, they are degraded by the highly selective ubiquitin-proteasome system. This process of protein quality control followed by proteasomal elimination of the misfolded protein is termed ER-associated degradation (ERAD), and it depends on an intricate interplay between the ER and the cytosol.

Keywords: Cdc48; ERAD; chaperones; endoplasmic reticulum–associated degradation; protein quality control; protein retrotranslocation; ubiquitin–proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytosol / metabolism
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum-Associated Degradation*
  • Humans
  • Models, Biological
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Folding
  • Proteolysis*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin / metabolism
  • Valosin Containing Protein / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • Valosin Containing Protein