PMID- 9337844
OWN - NLM
STAT- MEDLINE
DCOM- 19971113
LR  - 20240109
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 326 ( Pt 1)
IP  - Pt 1
DP  - 1997 Aug 15
TI  - Caspases: the executioners of apoptosis.
PG  - 1-16
AB  - Apoptosis is a major form of cell death, characterized initially by a series of 
      stereotypic morphological changes. In the nematode Caenorhabditis elegans, the 
      gene ced-3 encodes a protein required for developmental cell death. Since the 
      recognition that CED-3 has sequence identity with the mammalian cysteine protease 
      interleukin-1 beta-converting enzyme (ICE), a family of at least 10 related 
      cysteine proteases has been identified. These proteins are characterized by 
      almost absolute specificity for aspartic acid in the P1 position. All the 
      caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) 
      pentapeptide active-site motif. Capases are synthesized as inactive proenzymes 
      comprising an N-terminal peptide (prodomain) together with one large and one 
      small subunit. The crystal structures of both caspase-1 and caspase-3 show that 
      the active enzyme is a heterotetramer, containing two small and two large 
      subunits. Activation of caspases during apoptosis results in the cleavage of 
      critical cellular substrates, including poly(ADP-ribose) polymerase and lamins, 
      so precipitating the dramatic morphological changes of apoptosis. Apoptosis 
      induced by CD95 (Fas/APO-1) and tumour necrosis factor activates caspase-8 
      (MACH/FLICE/Mch5), which contains an N-terminus with FADD (Fas-associating 
      protein with death domain)-like death effector domains, so providing a direct 
      link between cell death receptors and the caspases. The importance of caspase 
      prodomains in the regulation of apoptosis is further highlighted by the 
      recognition of adapter molecules, such as RAIDD [receptor-interacting protein 
      (RIP)-associated ICH-1/CED-3-homologous protein with a death domain]/CRADD 
      (caspase and RIP adapter with death domain), which binds to the prodomain of 
      caspase-2 and recruits it to the signalling complex. Cells undergoing apoptosis 
      following triggering of death receptors execute the death programme by activating 
      a hierarchy of caspases, with caspase-8 and possibly caspase-10 being at or near 
      the apex of this apoptotic cascade.
FAU - Cohen, G M
AU  - Cohen GM
AD  - MRC Toxicology Unit, University of Leicester, U.K.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Apoptosis/drug effects/genetics
MH  - Cysteine Endopeptidases/*chemistry/genetics/*physiology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Multigene Family
MH  - Structure-Activity Relationship
PMC - PMC1218630
EDAT- 1997/08/15 00:00
MHDA- 1997/10/24 00:01
PMCR- 1998/02/15
CRDT- 1997/08/15 00:00
PHST- 1997/08/15 00:00 [pubmed]
PHST- 1997/10/24 00:01 [medline]
PHST- 1997/08/15 00:00 [entrez]
PHST- 1998/02/15 00:00 [pmc-release]
AID - 10.1042/bj3260001 [doi]
PST - ppublish
SO  - Biochem J. 1997 Aug 15;326 ( Pt 1)(Pt 1):1-16. doi: 10.1042/bj3260001.