Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins.
Many misfolded endoplasmic reticulum (ER) proteins are eliminated by ERAD, a process in which substrates are polyubiquitylated and moved into the cytosol for proteasomal degradation. We have identified in S. cerevisiae distinct ubiquitin-ligase complexes that define different ERAD pathways. Proteins with misfolded ER-luminal domains use the ERAD-L pathway, in which ... the Hrd1p/Hrd3p ligase forms a near stoichiometric membrane core complex by binding to Der1p via the linker protein Usa1p. This core complex associates through Hrd3p with Yos9p, a substrate recognition protein in the ER lumen. Substrates with misfolded intramembrane domains define a pathway (ERAD-M) that differs from ERAD-L by being independent of Usa1p and Der1p. Membrane proteins with misfolded cytosolic domains use the ERAD-C pathway and are directly targeted to the Doa10p ubiquitin ligase. All three pathways converge at the Cdc48p ATPase complex. These results lead to a unifying concept for ERAD that may also apply to mammalian cells.
Mesh Terms:
Adenosine Triphosphatases, Carrier Proteins, Cell Cycle Proteins, Endoplasmic Reticulum, Fungal Proteins, Ligases, Membrane Glycoproteins, Membrane Proteins, Models, Biological, Protein Folding, Protein Structure, Tertiary, Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity, Ubiquitin, Ubiquitin-Protein Ligases
Adenosine Triphosphatases, Carrier Proteins, Cell Cycle Proteins, Endoplasmic Reticulum, Fungal Proteins, Ligases, Membrane Glycoproteins, Membrane Proteins, Models, Biological, Protein Folding, Protein Structure, Tertiary, Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity, Ubiquitin, Ubiquitin-Protein Ligases
Cell
Date: Jul. 28, 2006
PubMed ID: 16873066
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