title: Polycystic liver disease is a disorder of cotranslational protein processing.
abstract: Autosomal-dominant polycystic liver disease (PCLD) is a rare disorder that is characterized by the progressive development of fluid-filled biliary epithelial cysts in the liver. Positional cloning has identified two genes that are mutated in patients with polycystic liver disease, PRKCSH and SEC63, which encode the beta-subunit of glucosidase II and Sec63, respectively. Both proteins are components of the molecular machinery involved in the translocation, folding and quality control of newly synthesized glycoproteins in the endoplasmic reticulum. Most mutations are truncating and probably lead to a complete loss of the corresponding proteins and the defective processing of a key regulator of biliary cell growth. The finding that PCLD is caused by proteins involved in oligosaccharide processing was unexpected and implicates a new avenue for research into neocystogenesis, and might ultimately result in the identification of novel therapeutic drugs.
authors.affiliation: The Department of Medicine, Division of Gastroenterology and Hepatology, University Medical Center St. Radboud, 6500 HB Nijmegen, The Netherlands. JoostPHDrenth@CS.com
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Jose A
authors.initials: JA
authors.lastname: Martina
authors.forename: Rolf
authors.initials: R
authors.lastname: van de Kerkhof
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: Jan B M J
authors.initials: JB
authors.lastname: Jansen
mesh_terms: D002135:Calcium-Binding Proteins; D003560:Cysts / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005959:Glucosidases; D006031:Glycosylation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D046188:Protein Modification, Translational; D016601:RNA-Binding Proteins; D000520:alpha-Glucosidases / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C487464:SEC63 protein, human; C034251:4-nitrophenyl-alpha-glucosidase; D005959:Glucosidases; C070368:PRKCSH protein, human; D000520:alpha-Glucosidases