• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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.

Pubmed ID: 16873066

Authors

  • Carvalho P
  • Goder V
  • Rapoport TA

Journal

Cell

Publication Data

July 28, 2006

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM052586

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