ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B

被引:282
作者
Duan, HJ
Orth, K
Chinnaiyan, AM
Poirier, GG
Froelich, CJ
He, WW
Dixit, VM
机构
[1] UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109
[2] UNIV LAVAL,CTR HOSP,DEPT MOLEC ENDOCRINOL,RES CTR,ST FOY,PQ G1V 4G2,CANADA
[3] NORTHWESTERN UNIV,SCH MED,EVANSTON,IL 60201
[4] EVANSTON HOSP CORP,DEPT MED,EVANSTON,IL 60201
[5] HUMAN GENOME SCI INC,ROCKVILLE,MD 20850
关键词
D O I
10.1074/jbc.271.28.16720
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:16720 / 16724
页数:5
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