Lack of β‐amyloid production in M19 cells deficient in site 2 processing of the sterol regulatory element binding proteins

FEBS Letters

Paganetti, Paolo A¹  Cescato, Renzo¹  Manni, Mara E¹ 

[1] Novartis Pharma Ltd., S.386.8.28, P.O. Box, CH-4002 Basel, Switzerland

关键词: Protein processing;    Proteolysis;    Amyloid precursor protein;    γ-Secretase;    Chinese hamster ovary cell;    Aβ;    β-amyloid;    APP;    amyloid precursor protein;    PBS;    phosphate buffered saline;    SDS-PAGE;    sodium dodecylsulfate-polyacrylamide gel electrophoresis;    SREBP;    sterol regulatory element binding protein;   

DOI  :  10.1016/S0014-5793(98)00469-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The processing of the amyloid precursor protein (APP) and the sterol regulatory element binding protein show remarkable analogies. Following a first lumenal cleavage, both proteins undergo a cleavage within the transmembrane domain by enzymatic activities named γ-secretase and S2P, respectively. We analyzed the processing of APP in the mutant Chinese hamster ovary (CHO) cell line M19 which lacks the S2P gene encoding for a putative metalloprotease. In these cells, we were not able to detect any β-amyloid production from endogenous or transiently overexpressed APP, although the transport of APP along the secretory pathway, its processing by α- and β-secretase, as well as its secretion were normal. This strongly suggests that the γ-secretase cleavage in M19 cells is severely impaired.

【 授权许可】

Unknown