CASPASES

Introduction

Caspases are a family of intracellular Cysteine Proteases that play a central role in the initiation and execution of programmed cell death. The term caspases is a short form for Cystein Aspartate-specific Proteases: their catalytical activity depends on a critical cystein-residue within a highly conserved active-site pentapeptide QACRG, and the caspases specifically cleave their substrates after Asp residues (also the serine-protease granzyme B has specificity for Asp in the P1 position of substrates).

So far, 10 different members of the caspase-family were identified in mammals. According to a unified nomenclature, the caspases are referred to in the order of their publication: so Caspase-1 is ICE (Interleukin-1beta-Converting Enzyme)¸ the first aspartate-specific cystein protease described.
The following table lists the 10 known caspases and some additional information:

 

Caspase

Other names

Size and subunits

Substrates

Cleavage motif

Caspase-1

ICE

proenzyme:
45158 Da,
active:
p20 and p10

 Pro-IL-1ß
U1-70 kDa ?
PARP ?
Pro-Caspases-1, -3, -4		 YVHD - A
DGPD - G
DEVD- G  

Caspase-2

Nedd2, ICH-1

proenzyme:
48855 Da,
active:
p12/14 and p19

 PARP ? DEVD - G

Caspase-3

CPP32, YAMA, apopain

proenzyme:
31594 Da,
active:
p17 and p12

 PARP
U1-70 kDa
DNA-PK (cs)
Protein Kinase C delta
Huntingtin
SREBP-1 and SREBP-2
Rb
DNA Frag. Factor (DFF)		 DEVD - G
DGPD - G
DEVD - N
DMQD - N
DXXD
DEPD - S
DEAD - G
DETD-S/DAVD-T

Caspase-4

ICE(rel)II, TX, ICH-2

proenzyme:
43262 Da,
active:
p?? and p??

 Similiar to Caspase-1 substrate specificity ???  

Caspase-5

ICE(rel)III, TY

proenzyme:
47814 Da,
active:
p20 and p10

    

Caspase-6

Mch2

proenzyme:
33409 Da,
active:
p18 and p11

 Lamin A
PARP ?
U1-70 kDa ?		 VEID - N
DEVD - G
DGPD - G

Caspase-7

Mch3, ICE-LAP3, CMH-1

proenzyme:
34276 Da,
active:
p20 and p11

 PARP
Substrate range like
Caspase-3 ???		 DEVD - G

 

Caspase-8

MACH, FLICE, Mch5

proenzyme:
55391 Da,
active:
p18 and p10

 All other Pro-Caspases  

Caspase-9

ICE-LAP6, Mch6

proenzyme:
46322 Da,
active:
p35 and p10

 PARP ?
Pro-Caspase-3		 DEVD - G

Caspase-10

Mch4

proenzyme:
58878 Da,
active:
p23/17 and p12

 All other Pro-Caspases  

The contents of that Table were combined from: Alnemri, E.S., 1997, J. Cell. Biochem., 64: 33-42 and Cohen, G.M., 1997, Biochem. J., 326: 1-16) and the SWISS PROT databank. The question mark signals that the physiological relevance is not yet clear.

Phylogenetic analysis of the caspases revealed that the caspases belong to three different subfamilies: The ICE subfamily: caspases-1, -4, and -5; The CED-3/CPP32 subfamily: caspases-3, -6, -7, -8, -9 and -10; The ICH-1/Nedd2 family: caspase-2.

References for all sections about Caspases (mainly Reviews):

Cohen, 1997, Biochem. J., 326: 1-16 (Review);
Alnemri, 1997, J. Cell. Biochem., 64: 33-42 (Review);
Salvesen/Dixit, 1997, Cell, 91: 443-446 (Review);
Wyllie, 1997, Br. Med. Bull., vol.53, No.3 (Review);
Alnemri et al., 1996, Cell, 87: p121 (Nomenclature);