Abstract
Proteases not only play a fundamental role in numerous physiological processes, but are also involved in several human diseases including Alzheimer's disease (AD). A key protease implicated in AD is the so far unidentified gamma-secretase, which cleaves the membrane-bound beta-amyloid precursor protein (betaAPP) at the C-terminus of its amyloid domain within the membrane to release the neurotoxic amyloid beta-peptide. In order to allow the isolation of proteases, which specifically cleave membrane-bound substrates within or in the vicinity of a transmembrane domain, we developed a reporter gene assay in Saccharomyces cerevisiae. This assay may allow the identification of genes encoding target proteases that specifically cleave membrane bound substrates by transforming expression libraries.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amyloid Precursor Protein Secretases
-
Aspartic Acid Endopeptidases
-
Binding Sites
-
Caspase 3
-
Caspases / genetics
-
DNA-Binding Proteins
-
Endopeptidases / analysis*
-
Endopeptidases / genetics
-
Endopeptidases / metabolism
-
Fungal Proteins / genetics
-
Genes, Reporter
-
Membrane Proteins / analysis
-
Membrane Proteins / metabolism*
-
Plasmids
-
Proteins / genetics
-
Receptors, Notch
-
Recombinant Fusion Proteins / biosynthesis
-
Recombinant Fusion Proteins / genetics
-
Saccharomyces cerevisiae / genetics
-
Saccharomyces cerevisiae / metabolism
-
Saccharomyces cerevisiae Proteins*
-
Substrate Specificity
-
Transcription Factors / genetics
Substances
-
DNA-Binding Proteins
-
Fungal Proteins
-
GAL4 protein, S cerevisiae
-
Membrane Proteins
-
Proteins
-
Receptors, Notch
-
Recombinant Fusion Proteins
-
Saccharomyces cerevisiae Proteins
-
Transcription Factors
-
Amyloid Precursor Protein Secretases
-
Endopeptidases
-
CASP3 protein, human
-
Caspase 3
-
Caspases
-
Aspartic Acid Endopeptidases
-
BACE1 protein, human