Retrograde protein translocation: ERADication of secretory proteins in health and disease.
Eukaryotic cells have a complex degradation machinery that eliminates misfolded or unassembled secretory proteins from the endoplasmic reticulum (ER). The proteins are retained in an ER/pre-Golgi compartment and then hydrolysed by the cytosolic ubiquitin-proteasome system. This requires retrograde translocation of proteins from the ER back to the cytoplasm, which is mediated by Sec61, the central component of the ER protein-import channel. This proteolytic pathway prevents a potentially lethal aggregation of secretory proteins; however, several viruses misuse it to escape detection, and bacterial and plant toxins might also exploit it. Underactive or overactive ER degradation machinery contributes to the pathogenesis of several severe human diseases.
Plemper
R K
RK
Institut für Biochemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
Wolf
D H
DH
D001693:Biological Transport, Active; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003550:Cystic Fibrosis / Q000209:etiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism; D014777:Virus Diseases / Q000209:etiology
D009097:Multienzyme Complexes; D011506:Proteins; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex