PMID- 10638761
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20161124
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 403
IP  - 6765
DP  - 2000 Jan 6
TI  - Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by 
      amyloid-beta.
PG  - 98-103
AB  - Apoptosis, or cellular suicide, is important for normal development and tissue
      homeostasis, but too much or too little apoptosis can also cause disease. The
      family of cysteine proteases, the so- called caspases, are critical mediators of 
      programmed cell death, and thus far 14 family members have been identified. Some 
      of these, such as caspase-8, mediate signal transduction downstream of death
      receptors located on the plasma membrane. Others, such as caspase-9, mediate
      apoptotic signals after mitochondrial damage. Stress in the endoplasmic reticulum
      (ER) can also result in apoptosis. Here we show that caspase-12 is localized to
      the ER and activated by ER stress, including disruption of ER calcium homeostasis
      and accumulation of excess proteins in ER, but not by membrane- or
      mitochondrial-targeted apoptotic signals. Mice that are deficient in caspase-12
      are resistant to ER stress-induced apoptosis, but their cells undergo apoptosis
      in response to other death stimuli. Furthermore, we show that
      caspase-12-deficient cortical neurons are defective in apoptosis induced by
      amyloid-beta protein but not by staurosporine or trophic factor deprivation.
      Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to 
      amyloid-beta neurotoxicity.
FAU - Nakagawa, T
AU  - Nakagawa T
AD  - Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, 
      USA.
FAU - Zhu, H
AU  - Zhu H
FAU - Morishima, N
AU  - Morishima N
FAU - Li, E
AU  - Li E
FAU - Xu, J
AU  - Xu J
FAU - Yankner, B A
AU  - Yankner BA
FAU - Yuan, J
AU  - Yuan J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Cytotoxins)
RN  - 11089-65-9 (Tunicamycin)
RN  - EC 3.4.22.- (CASP12 protein, human)
RN  - EC 3.4.22.- (Casp12 protein, mouse)
RN  - EC 3.4.22.- (Casp12 protein, rat)
RN  - EC 3.4.22.- (Caspase 12)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
CIN - Nat Rev Mol Cell Biol. 2013 Jul;14(7):404. PMID: 23756618
MH  - Alzheimer Disease/enzymology/etiology
MH  - Amyloid beta-Peptides/*metabolism/toxicity
MH  - Animals
MH  - *Apoptosis
MH  - Caspase 12
MH  - Caspases/genetics/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/drug effects
MH  - Cytotoxins/metabolism/toxicity
MH  - Endoplasmic Reticulum/drug effects/*enzymology
MH  - Enzyme Activation
MH  - HeLa Cells
MH  - Humans
MH  - Kidney/cytology/drug effects
MH  - Mice
MH  - Mice, Knockout
MH  - Mutagenesis
MH  - Neurons/physiology
MH  - PC12 Cells
MH  - Rats
MH  - Thymus Gland/cytology
MH  - Tunicamycin/pharmacology
EDAT- 2000/01/19 09:00
MHDA- 2001/03/23 10:01
CRDT- 2000/01/19 09:00
PHST- 2000/01/19 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 2000/01/19 09:00 [entrez]
AID - 10.1038/47513 [doi]
PST - ppublish
SO  - Nature. 2000 Jan 6;403(6765):98-103. doi: 10.1038/47513.