ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B.
Members of the ICE/Ced-3 gene family are likely effector components of the cell death machinery. Here, we characterize a novel member of this family designated ICE-LAP6. By phylogenetic analysis, ICE-LAP6 is classified into the Ced-3 subfamily which includes Ced-3, Yama/CPP32/apopain, Mch2, and ICE-LAP3/Mch3/CMH-1. Interestingly, ICE-LAP6 contains an active site QACGG pentapeptide, rather than the QACRG pentapeptide shared by other family members. Overexpression of ICE-LAP6 induces apoptosis in MCF7 breast carcinoma cells. More importantly, ICE-LAP6 is proteolytically processed into an active cysteine protease by granzyme B, an important component of cytotoxic T cell-mediated apoptosis. Once activated, ICE-LAP6 is able to cleave the death substrate poly(ADP-ribose) polymerase into signature apoptotic fragments.
Duan
H
H
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Orth
K
K
Chinnaiyan
A M
AM
Poirier
G G
GG
Froelich
C J
CJ
He
W W
WW
Dixit
V M
VM
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D053804:Granzymes; D015801:Helminth Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D015801:Helminth Proteins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1