Polycystic liver disease is a disorder of cotranslational protein processing

• Published in: Trends in molecular medicine Vol. 11; no. 1; pp. 37 - 42
• Main Authors: Drenth, Joost P.H., Martina, Jose A., Kerkhof, Rolf van de, Bonifacino, Juan S., Jansen, Jan B.M.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2005
• Subjects: alpha-Glucosidases - genetics; alpha-Glucosidases - metabolism; Cysts - genetics; Cysts - metabolism; Cysts - therapy; Endoplasmic Reticulum - metabolism; Glucosidases; Glycosylation; Humans; Intracellular Signaling Peptides and Proteins; Liver Diseases - genetics; Liver Diseases - metabolism; Liver Diseases - therapy; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutation; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein Modification, Translational
• ISSN: 1471-4914; 1471-499X
• DOI: 10.1016/j.molmed.2004.11.004

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 β-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.