An in vivo assay for the identification of target proteases which cleave membrane‐associated substrates

FEBS Letters

Haass, Christian¹  Steiner, Harald¹  Pesold, Brigitte¹ 

[1] Central Institute of Mental Health, Department of Molecular Biology, J5, 68159 Mannheim, Germany

关键词: Alzheimer's disease;    Amyloid β-peptide;    Notch;    Proteolytic processing;    γ-Secretase;    Aβ;    amyloid β-peptide;    βAPP;    β-amyloid precursor protein;    AD;    Alzheimer's disease;    β-gal;    β-galactosidase;    NICD;    Notch intracellular cytoplasmic domain;    PARP;    poly(ADP-ribose) polymerase;    PS;    presenilin;   

DOI  :  10.1016/S0014-5793(99)01627-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown