An in vivo assay for the identification of target proteases which cleave membrane-associated substrates
FEBS Lett 463(3): 245-9
|Type of Publication:||Journal Article|
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 γ-secretase, which cleaves the membrane-bound β-amyloid precursor protein (βAPP) at the C-terminus of its amyloid domain within the membrane to release the neurotoxic amyloid β-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.