PMID- 10069390
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 445
IP  - 1
DP  - 1999 Feb 19
TI  - Identification of caspases that cleave presenilin-1 and presenilin-2. Five
      presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases.
PG  - 149-54
AB  - Mutations in the presenilin (PS) genes PSI 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 PSI after residues ENDD329 and to a lesser extent after residues
      AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on
      AQRD341. 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 D326SYD329. 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 PSI to caspase-mediated cleavage. This suggests that AD
      pathogenesis associated with PS1 missense mutations cannot be explained by a
      change in caspase-dependent processing.
FAU - van de Craen, M
AU  - van de Craen M
AD  - Department of Molecular Biology, Flanders Interuniversity Institute for
      Biotechnology and University of Gent, Belgium.
FAU - de Jonghe, C
AU  - de Jonghe C
FAU - van den Brande, I
AU  - van den Brande I
FAU - Declercq, W
AU  - Declercq W
FAU - van Gassen, G
AU  - van Gassen G
FAU - van Criekinge, W
AU  - van Criekinge W
FAU - Vanderhoeven, I
AU  - Vanderhoeven I
FAU - Fiers, W
AU  - Fiers W
FAU - van Broeckhoven, C
AU  - van Broeckhoven C
FAU - Hendriks, L
AU  - Hendriks L
FAU - Vandenabeele, P
AU  - Vandenabeele P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (PSEN2 protein, human)
RN  - 0 (Presenilin-1)
RN  - 0 (Presenilin-2)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Caspases/*metabolism
MH  - Humans
MH  - Membrane Proteins/genetics/*metabolism
MH  - Presenilin-1
MH  - Presenilin-2
MH  - Rabbits
EDAT- 1999/03/09 00:00
MHDA- 1999/03/09 00:01
CRDT- 1999/03/09 00:00
PHST- 1999/03/09 00:00 [pubmed]
PHST- 1999/03/09 00:01 [medline]
PHST- 1999/03/09 00:00 [entrez]
AID - S0014-5793(99)00108-8 [pii]
AID - 10.1016/s0014-5793(99)00108-8 [doi]
PST - ppublish
SO  - FEBS Lett. 1999 Feb 19;445(1):149-54. doi: 10.1016/s0014-5793(99)00108-8.