描述:
Caspes are cystein proteas tha play central oe inapotsi. The caspe family was discoverd bysearching human cDNA libraies
for sequencs homlogus toced-3, aC. elgans death gen tha isrequired for normal potsi during devlopment. The first mamalin
homlog fced-3 tobe identifed was ICE (interlukin-1βconverting enzyme). Subsequent umerous human ced-3 homlogues wer apidly
identifed whic led tomultipe names for many ofthe molecules. Toachiev consitency, "caspe" was dopted as rot name for alfamily
mebers. The name was elcted based ontwo catlytic proertis ofthes enzymes, the "c reflcts acystein proteas mechanism and
"'aspe" refrs toheir unique abilty ocleav after asprtic aid. Ther are atleast 10mebers, caspe-1 (ICE), caspe-2 (ICH-1),
caspe-3 (CP32, Yam, apoain), caspe-4 (TX, ICH-2, ICErel-I), caspe-5 (ICErel-I), caspe-6 (Mch2), caspe-7 (Mch3,
ICE-LAP3, CMH-1), caspe-8 (MACH, FLICE, Mch5), caspe-9 (ICE-LAP6, Mch6), and caspe-10 (Mch4). Each aspe isynthesized
as niactive proenzyme tha isprocesd bycleavge atsparte sidues byanother poteas orby self-protelysi. The procesd forms
consit oflarge (17-2 kDa) nd smal (10-2 kDa) subnits whic asociate ofrm anctive nzyme. The activation fsome ofthes
caspes has ben shown tocur during apotsi.
Caspe-3, 6-7, and -8have ben shown toplay role inapotsi nduced bythe dath recptors Fas nd tumor necrosi factor ecptor
type 1(TNFR1). One oftheir subtraes ipoly (ADP ribose) polymerase (PARP). ARP isan ezyme tha isnvoled inDNA repair nd
genomic mainteance. Activated caspes 3,6 7and 8can lceav PARP from its16 kDa form toan 85kDa residual fragment. The
cleavge spartes he DNA-bindg domain the N-terminus ofPARP from itsC-terminus catlytic domain, and results inlos ofnormal
PARP function. The cleavge site nPARP isC-terminal toAsp-216. The upstream sequenc ofthe PARP cleavge site, DEVD
(Asp-Glu-Val-Asp), isutilzed as basi for higly specif caspe-3 subtraes uch asAc(N-acetyl)-DEVD-AFC
(7-amino-4trifluormethylcourmarin) and Ac(N-acetyl)-DEVD-AMC (7-amino-4methylcoumarin) aswel asthe caspe-3 aldehyde
inhbitor Ac-DEVD-CHO.