The final moments of misfolded proteins en route to the proteasome.
Protein homeostasis in the endoplasmic reticulum (ER) in eukaryotic cells is maintained by a conserved quality control system named ER-associated degradation (ERAD). The ERAD system retains misfolded or unassembled polypeptides in the ER, retrotranslocates them into the cytosol for degradation by the ubiquitin proteasome system. Central to the ERAD process is the AAA+ (ATPase associated with various cellular activities), ATPase p97/VCP (also known as Cdc48p in yeast), and the proteasome. p97/VCP couples ATP hydrolysis to the extraction of misfolded proteins from retrotranslocation sites and subsequently targets them for degradation, but how p97/VCP hands substrate off to the proteasome is unclear. Recent studies suggest that p97/VCP may either directly translocate polypeptides into the proteolytic compartment of the 20S subcomplex, or use a set of shuttling factors to deliver retrotranslocated polypeptides to the proteasome.
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland.
Ting
T
Zhang
Yihong
Y
Ye
D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D060746:Endoplasmic Reticulum-Associated Degradation; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D021381:Protein Transport; D059748:Proteolysis; D057149:Ubiquitinated Proteins / Q000378:metabolism*; D054875:Ubiquitination
D009687:Nuclear Proteins; D057149:Ubiquitinated Proteins; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C404942:p97 ATPase