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caspase-3; CPP32/YAMA; PARP cleavage protease; apopain (CASP3, CPP32)
Function:
- role in the activation cascade of caspases responsible for apoptosis execution
- at the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-gly-217' bond
- cleaves sterol regulatory element binding proteins (SREBPs) & activates them; cleaves between the basic helix-loop-helix leucine zipper domain & the membrane attachment domain
- cleaves & activates caspase-6, caspase-7 & caspase-9
- involved in the cleavage of huntingtin
- cleavage by granzyme B, caspase-6, caspase-8 & caspase-10 generates the two active subunits
- additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease
- S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines & denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity
- Fas thus activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol
- strict requirement for an Asp residue at positions P1 & P4
- preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a hydrophobic amino-acid residue at P2 & a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position
Inhibition:
- inhibited by isatin sulfonamides
Structure:
- heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kD (p17) & a 12 kD (p12) subunit
- active heterodimers between the small subunit of caspase-7 protease & the large subunit of caspase-3 also occur & vice versa
- belongs to the peptidase C14 family
Compartment: cytoplasm
Expression:
- expressed in lung, spleen, heart, liver & kidney > brain & skeletal muscle, & low in testis
- also found in many cell lines
- highest expression in cells of the immune system
Interactions
molecular events
Related
apoptotic protease-activating factor 1; APAF-1 (APAF1, KIAA0413)
caspase 3 substrates
Specific
procpp32/yama
General
caspase; cysteinyl aspartate-specific proteinase; ICE/CED3 family protease
phosphoprotein
Properties
SIZE: entity length = 277 aa
MW = 32 kD
COMPARTMENT: cytoplasm
MOTIF: Ser phosphorylation site {S26}
histidine residue {H121}
cysteine residue {C163}
References
- Martin SJ, Green DR.
Protease activation during apoptosis: death by a thousand cuts?
Cell. 1995 Aug 11;82(3):349-52. Review. No abstract available.
PMID: 7634323
- UniProt :accession P42574
Databases & Figures
OMIM 600636
UniProt P42574
Pfam PF00656
Entrez Gene 836
KEGG correlations
signaling pathways: caspases -> APP