Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-6-28
pubmed:abstractText
Autosomal dominant polycystic liver disease results from mutations in PRKCSH or SEC63. The respective gene products, glucosidase II? and SEC63p, function in protein translocation and quality control pathways in the endoplasmic reticulum. Here we show that glucosidase II? and Sec63p are required in mice for adequate expression of a functional complex of the polycystic kidney disease gene products, polycystin-1 and polycystin-2. We find that polycystin-1 is the rate-limiting component of this complex and that there is a dose-response relationship between cystic dilation and levels of functional polycystin-1 following mutation of Prkcsh or Sec63. Reduced expression of polycystin-1 also serves to sensitize the kidney to cyst formation resulting from mutations in Pkhd1, the recessive polycystic kidney disease gene. Finally, we show that proteasome inhibition increases steady-state levels of polycystin-1 in cells lacking glucosidase II? and that treatment with a proteasome inhibitor reduces cystic disease in orthologous gene models of human autosomal dominant polycystic liver disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1546-1718
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
639-47
pubmed:meshHeading
pubmed-meshheading:21685914-Animals, pubmed-meshheading:21685914-Apoptosis, pubmed-meshheading:21685914-Blotting, Western, pubmed-meshheading:21685914-Cell Proliferation, pubmed-meshheading:21685914-Cysts, pubmed-meshheading:21685914-Female, pubmed-meshheading:21685914-Glucosidases, pubmed-meshheading:21685914-Immunoenzyme Techniques, pubmed-meshheading:21685914-Immunoprecipitation, pubmed-meshheading:21685914-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:21685914-Liver Diseases, pubmed-meshheading:21685914-Male, pubmed-meshheading:21685914-Mice, pubmed-meshheading:21685914-Mice, Inbred C57BL, pubmed-meshheading:21685914-Mice, Transgenic, pubmed-meshheading:21685914-Mutation, pubmed-meshheading:21685914-Polycystic Kidney Diseases, pubmed-meshheading:21685914-Receptors, Cell Surface, pubmed-meshheading:21685914-TRPP Cation Channels
pubmed:year
2011
pubmed:articleTitle
A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation.
pubmed:affiliation
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural