Ubiquitin receptors and ERAD: a network of pathways to the proteasome.
The elimination of misfolded proteins, known as protein quality control, is an essential cellular process. Removal of misfolded proteins from the secretory pathway depends on their recognition in the endoplasmic reticulum (ER) followed by their retrograde transport into the cytosol for degradation. The AAA-ATPase Cdc48/p97 facilitates the translocation of misfolded ER-proteins into the cytosol. Cdc48/p97 can dock onto the ER-membrane via direct interaction with ER-membrane proteins and/or indirectly via its substrate-recruiting cofactors, which interact with the ubiquitylated substrates at the membrane. This tight interaction in conjunction with the conformational changes induced upon ATP hydrolysis within Cdc48/p97 is thought to provide the driving force for the translocation reaction. Subsequently, a series of protein-protein interactions between the Cdc48/p97 complex, its cofactors, and the ubiquitylated substrates is instrumental for the proper delivery of the ER substrates to the proteasome. These protein-protein interactions are governed mainly by ubiquitin-fold and ubiquitin-binding domains.
Raasi
Shahri
S
Fachbereich Biologie, Universitaet Konstanz, Universitaetsstrasse 10, 78457 Konstanz, Germany. shahri.raasi@uni-konstanz.de
Wolf
Dieter H
DH
D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017510:Protein Folding; D054875:Ubiquitination; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C404942:p97 ATPase; D000074405:Valosin Containing Protein