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Identification of caspases that cleave presenilin‐1 and presenilin‐2
Author(s) -
van de Craen Marc,
de Jonghe Chris,
van den Brande Ilse,
Declercq Wim,
van Gassen Geert,
van Criekinge Wim,
Vanderhoeven Inge,
Fiers Walter,
van Broeckhoven Christine,
Hendriks Lydia,
Vandenabeele Peter
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00108-8
Subject(s) - caspase , presenilin , proteolysis , cleavage (geology) , missense mutation , caspase 3 , caspase 2 , apoptosis , biology , microbiology and biotechnology , chemistry , biochemistry , alzheimer's disease , gene , programmed cell death , mutation , enzyme , medicine , disease , paleontology , fracture (geology)
Mutations in the presenilin (PS) genes PS1 and PS2 are involved in Alzheimer's disease (AD). Recently, apoptosis‐associated cleavage of PS proteins was identified. Here we demonstrate that PS1 as well as PS2 are substrates for different members of the caspase protein family. Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase‐8, ‐6 and ‐11, cleaved PS1 after residues ENDD 329 and to a lesser extent after residues AQRD 341 . A second group consisting of caspase‐3, ‐7 and ‐1 acted uniquely on AQRD 341 . Importantly, these two cleavage sites were also recognized by caspases in the C‐terminal PS1 fragment produced by constitutive proteolysis. In decreasing order of activity, caspase‐8, ‐3, ‐1, ‐6 and ‐7 proteolysed PS2 at the recognition site D 326 SYD 329 . Caspase‐8 and ‐3 exhibited the highest proteolytic activity on both PS1 and PS2. PS1 and PS2 were not hydrolyzed by caspase‐2 and PS2 also not by caspase‐11. None of five missense mutations affected the sensitivity of PS1 to caspase‐mediated cleavage. This suggests that AD pathogenesis associated with PS1 missense mutations cannot be explained by a change in caspase‐dependent processing.