Caspase-7 gene disruption reveals an involvement of the enzyme during the early stages of apoptosis

被引:35
作者
Korfali, N
Ruchaud, S
Loegering, D
Bernard, D
Dingwall, C
Kaufmann, SH
Earnshaw, WC
机构
[1] Univ Edinburgh, Inst Cell & Mol Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland
[2] Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA
[3] Univ Paris 07, Unite Format Rech Biol & Sci Nat, Magistere Genet, F-75005 Paris, France
[4] GlaxoSmithKline, Neurol Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England
基金
英国惠康基金;
关键词
D O I
10.1074/jbc.M306277200
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
Caspases play a key role during apoptotic execution. In an attempt to elucidate the specific role of caspase-7 we generated a chicken DT40 cell line in which both alleles of the gene were disrupted. Viability assays showed that caspase-7(-/-) clones are more resistant to the common apoptosis-inducing drugs etoposide and staurosporine. Caspase-7(-/-) cells show a delay in phosphatidylserine externalization and DNA fragmentation as well as cleavage of the caspase substrates poly(ADP-ribose) polymerase 1 and lamins B1 and B2. Caspase affinity labeling and activity assays indicated that deficient cells exhibit a delay in caspase activation compared with wild type DT40 cells, providing an explanation for the differences in apoptotic execution between caspase-7 null and wild type DT40 cells. These results strongly suggest that caspase-7 is involved earlier than other effector caspases in the apoptotic execution process in DT40 B lymphocytes.
引用
收藏
页码:1030 / 1039
页数:10
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