Differential inhibitory effects of CrmA, P35, IAP and three mammalian IAP homologues on apoptosis in NIH3T3 cells following various death stimuli

被引:25
作者
Dorstyn, L [1 ]
Kumar, S [1 ]
机构
[1] INST MED & VET SCI,HANSON CTR CANC RES,ADELAIDE,SA 5000,AUSTRALIA
基金
英国医学研究理事会; 英国惠康基金;
关键词
ICE; Nedd2; CPP32; caspase; P35; IAP;
D O I
10.1038/sj.cdd.4400281
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
We have investigated the effects of expression of the viral proteins CrmA, P35 and IAP, and the three mammalian IAP homologues (MIHA, MIHB and MIHC), on the regulation of apoptosis induced by either the overexpression of caspases (ICE, CPP32 and Nedd2), by serum-deprivation, or by gamma-irradiation in NIH3T3 fibroblasts. As previously shown, CrmA strongly inhibited ICE-induced apoptosis but was ineffective against Nedd2- or CPP32-mediated apoptosis, P35, IAP and MIHA protected cells from apoptosis induced by the three caspases to varying extents but MIHB and MIHC were largely ineffective, NIH3T3 cells expressing P35 and MIHA, but not IAP, CrmA, MIHB and MIHC, showed enhanced cell survival under serum-deprived conditions, In addition, P35, CrmA and MIHA could provide substantial protection against death induced by gamma-irradiation. These results suggest the presence of multiple apoptotic pathways with differential sensitivity to various naturally occurring apoptosis inhibitors.
引用
收藏
页码:570 / 579
页数:10
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