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

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Abstract
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.