Hawkins C J, Ekert P G, Uren A G, Holmgreen S P, Vaux D L
The Walter and Eliza Hall Institute for Medical Research, Post Office Royal Melbourne Hospital, Victoria, 3050, Australia.
Cell Death Differ. 1998 Jul;5(7):569-76. doi: 10.1038/sj.cdd.4400389.
IAPs were identified as baculoviral proteins that could inhibit the apoptotic response of insect cells to infection. Of the viral IAPs, OpIAP and CpIAP can inhibit apoptosis, whereas AcIAP cannot. OpIAP and some mammalian homologues can inhibit mammalian cell death. Two mammalian IAPs bind to TNFRII associated factors (TRAFs), but the significance of this is unclear. Here we show that Drosophila cellular IAPs and two baculoviral IAPs (OpIAP and CpIAP) can inhibit mammalian cell death induced by overexpression of Caspases 1 and 2. IAPs must act on conserved components of the apoptotic mechanism, but as none of these IAPs could bind TRAF proteins, TRAFs are not likely to be important for IAP mediated apoptosis inhibition. As OpIAP protected against death induced by ligation of TNF receptor family members, but not by factor nor serum withdrawal from dependent cells, it can inhibit certain apoptotic pathways without affecting others.
凋亡抑制蛋白(IAPs)最初被鉴定为杆状病毒蛋白,能够抑制昆虫细胞对感染的凋亡反应。在病毒IAP中,OpIAP和CpIAP可以抑制凋亡,而AcIAP则不能。OpIAP和一些哺乳动物同源物可以抑制哺乳动物细胞死亡。两种哺乳动物IAP与肿瘤坏死因子受体II相关因子(TRAFs)结合,但其意义尚不清楚。在此我们表明,果蝇细胞IAP以及两种杆状病毒IAP(OpIAP和CpIAP)能够抑制由半胱天冬酶1和2过表达诱导的哺乳动物细胞死亡。IAPs必定作用于凋亡机制的保守组分,但由于这些IAPs均不能结合TRAF蛋白,TRAFs对于IAP介导的凋亡抑制作用可能并不重要。由于OpIAP可保护细胞免受肿瘤坏死因子受体家族成员连接诱导的死亡,但不能保护细胞免受因子或依赖细胞血清撤除诱导的死亡,因此它可以抑制某些凋亡途径而不影响其他途径。