Seshagiri S, Miller L K
Department of Entomology, The University of Georgia, Athens, GA 30602, USA.
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13606-11. doi: 10.1073/pnas.94.25.13606.
We have investigated the ability of Sf-caspase-1 and two mammalian caspases, caspase-1 and caspase-3, to induce apoptosis in Spodoptera frugiperda Sf-21 insect cells. While the transient expression of the pro-Sf-caspase-1 did not induce apoptosis, expression of the pro-domain deleted form, p31, or coexpression of the two subunits of mature Sf-caspase-1, p19 and p12, induced apoptosis in Sf-21 cells. The behavior of Sf-caspase-1 resembled that of the closely related mammalian caspase, caspase-3, and contrasted with that of the mammalian caspase-1, the pro-form of which was active in inducing apoptosis in Sf-21 cells. The baculovirus caspase inhibitor P35 blocked apoptosis induced by active forms of all three caspases. In contrast, members of the baculovirus inhibitor of apoptosis (IAP) family failed to block active caspase-induced apoptosis. However, during viral infection, expression of OpIAP or CpIAP blocked the activation of pro-Sf-caspase-1 and the associated induction of apoptosis. Thus, the mechanism by which baculovirus IAPs inhibit apoptosis is distinct from the mechanism by which P35 blocks apoptosis and involves inhibition of the activation of pro-caspases like Sf-caspase-1.
我们研究了草地贪夜蛾半胱天冬酶-1（Sf-caspase-1）以及两种哺乳动物半胱天冬酶——半胱天冬酶-1和半胱天冬酶-3在草地贪夜蛾Sf-21昆虫细胞中诱导凋亡的能力。虽然前体Sf-caspase-1的瞬时表达未诱导凋亡，但前结构域缺失形式p31的表达或成熟Sf-caspase-1的两个亚基p19和p12的共表达诱导了Sf-21细胞凋亡。Sf-caspase-1的行为类似于密切相关的哺乳动物半胱天冬酶半胱天冬酶-3，与哺乳动物半胱天冬酶-1相反，后者的前体形式在诱导Sf-21细胞凋亡中具有活性。杆状病毒半胱天冬酶抑制剂P35阻断了所有三种半胱天冬酶活性形式诱导的凋亡。相比之下，杆状病毒凋亡抑制蛋白（IAP）家族成员未能阻断活性半胱天冬酶诱导的凋亡。然而，在病毒感染期间，OpIAP或CpIAP的表达阻断了前体Sf-caspase-1的激活以及相关的凋亡诱导。因此，杆状病毒IAP抑制凋亡的机制不同于P35阻断凋亡的机制，且涉及对像Sf-caspase-1这样的前体半胱天冬酶激活的抑制。
