The BioGRID | PUBLICATION VIEW

	Cell Jul (2006); 126(2):361-73
Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins-
Carvalho P, Goder V, Rapoport TA
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA-
Abstract: 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: 16873066]