Linked Life Data

12885769

Source:http://linkedlifedata.com/resource/pubmed/id/12885769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2003-10-27
pubmed:abstractText
The Presenilins are part of the gamma-secretase complex that is involved in the regulated intramembrane proteolysis of amyloid precursor protein and other type I integral membrane proteins. Nicastrin, Pen-2, and Aph1 are the other proteins of this complex. The Presenilins probably contribute the catalytic activity to the protease complex. However, several investigators reported normal Abeta-peptide generation in cells expressing Presenilins mutated at the putative catalytic site residue Asp-257, contradicting this hypothesis. Because endogenously expressed wild type Presenilin could contribute to residual gamma-secretase activity in these experiments, we have reinvestigated the problem by expressing mutated Presenilins in a Presenilin-negative cell line. We confirm that Presenilins with mutated Asp residues are catalytically inactive. Unexpectedly, these mutated Presenilins are still partially processed into amino- and carboxyl-terminal fragments by a "Presenilinase"-like activity. They are also able to rescue Pen-2 expression and Nicastrin glycosylation in Presenilin-negative cells and become incorporated into large approximately 440-kDa complexes as assessed by blue native gel electrophoresis. Our study demonstrates that the catalytic activity of Presenilin and its other functions in the generation, stabilization, and transport of the gamma-secretase complex can be separated and extends the concept that Presenilins are multifunctional proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43430-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12885769-Adenoviridae, pubmed-meshheading:12885769-Amyloid Precursor Protein Secretases, pubmed-meshheading:12885769-Animals, pubmed-meshheading:12885769-Aspartic Acid, pubmed-meshheading:12885769-Catalysis, pubmed-meshheading:12885769-Cell Line, pubmed-meshheading:12885769-Cell Membrane, pubmed-meshheading:12885769-Cell-Free System, pubmed-meshheading:12885769-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:12885769-Fibroblasts, pubmed-meshheading:12885769-Glycosylation, pubmed-meshheading:12885769-Humans, pubmed-meshheading:12885769-Membrane Glycoproteins, pubmed-meshheading:12885769-Membrane Proteins, pubmed-meshheading:12885769-Mice, pubmed-meshheading:12885769-Models, Genetic, pubmed-meshheading:12885769-Mutation, pubmed-meshheading:12885769-Presenilin-1, pubmed-meshheading:12885769-Presenilin-2, pubmed-meshheading:12885769-Transfection
pubmed:year
2003
pubmed:articleTitle
Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and Nicastrin glycosylation but remain catalytically inactive in the absence of wild type Presenilin.
pubmed:affiliation
Neuronal Cell Biology and Gene Transfer Laboratory, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB4) and K.U.Leuven, 3000 Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't