Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.60 (
caspase-7
)
920
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent evidence suggests that mammalian cysteine proteases related to Caenorhabditis elegans CED-3 are key components of mammalian programmed cell death or apoptosis. We have shown recently that the CPP32 and Mch2 alpha cysteine proteases cleave the apoptotic markers poly(ADP-ribose) polymerase (PARP) and lamins, respectively. Here we report the cloning of a new Ced-3/
interleukin 1 beta
-converting enzyme-related gene, designated
Mch3
, that encodes a protein with the highest degree of homology to CPP32 compared to other family members. An alternatively spliced isoform, named
Mch3
beta, was also identified. Bacterially expressed recombinant
Mch3
has intrinsic autocatalytic/autoactivation activity. The specific activity of
Mch3
alpha toward the peptide substrate DEVD-7-amino-4-methylcoumarin and PARP resembles that of CPP32. Like
interleukin 1 beta
-converting enzyme and CPP32, the active
Mch3
alpha is made of two subunits derived from a precursor (proMch3 alpha). It was of interest that recombinant CPP32-p17 subunit can form an active heteromeric enzyme complex with recombinant
Mch3
alpha-p12 subunit and vice versa, as determined by the ability of the heteromeric complexes to induce apoptosis in Sf9 cells. These data suggest that proMch3 alpha and proCPP32 can interact to form an active
Mch3
alpha/CPP32 heteromeric complex. We also provide evidence that CPP32 can efficiently cleave proMch3 alpha, but not the opposite, suggesting that
Mch3
alpha activation in vivo may depend in part on CPP32 activity. The high degree of conservation in structure and specific activity and the coexistence of
Mch3
alpha and CPP32 in the same cell suggests that the PARP cleavage activity observed during apoptosis cannot solely be attributed to CPP32 but could also be an activity of
Mch3
alpha.
...
PMID:Mch3, a novel human apoptotic cysteine protease highly related to CPP32. 852 91
We have identified and characterized a novel cysteine protease named
CMH-1
that is a new member of the
interleukin 1 beta
converting enzyme (ICE) family of proteases with substrate specificity for Asp-X.
CMH-1
has the highest similarity to CPP32 (52% amino acid identity) and MCH2 (31% identical).
CMH-1
shares conserved amino acid residues that form the core structure of ICE as well as those residues involved in catalysis and in the P1 aspartate binding. Overexpression of
CMH-1
in COS cells resulted in the processing of
CMH-1
and the induction of apoptosis of transfected cells. Coexpression of
CMH-1
with poly(ADP-ribose) polymerase (PARP) also resulted in a specific cleavage of PARP. Purified recombinant
CMH-1
cleaved PARP but not
interleukin 1 beta
precursor in vitro.
...
PMID:Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32. 856 22
