Inhibitor of Apoptosis (IAP)-like Protein Lacks a Baculovirus IAP Repeat (BIR) Domain and Attenuates Cell Death in Plant and Animal Systems
Inhibitor of Apoptosis (IAP)-like Protein Lacks a Baculovirus IAP Repeat (BIR) Domain and Attenuates Cell Death in Plant and Animal Systems
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DOI：
10.1074/jbc.m111.262204
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发表时间：
2011-12-09
影响因子：
4.8
通讯作者：
Lee, Sang Yeol
中科院分区：
文献类型：
--
作者：
Kim, Woe Yeon;Lee, Sun Yong;Lee, Sang Yeol
通过与已知凋亡抑制蛋白（IAP）的序列同源性分析，鉴定了一种新的拟南芥凋亡抑制蛋白。拟南芥IAP样蛋白（AtILP）含有C-末端的环指结构域，但缺乏杆状病毒IAP重复（BIR）结构域，这是必不可少的抗凋亡活性在其他IAP家族成员。AtILP在HeLa细胞中的表达通过半胱天冬酶活性的失活而赋予对肿瘤坏死因子（TNF）-α/ActD诱导的凋亡的抵抗。与AtILP的C-末端RING结构域（其不抑制半胱天冬酶-3的活性）相反，N-末端区域（尽管与已知的BIR结构域没有同源性）在体外有效地抑制半胱天冬酶-3的活性并阻断TNF-α/ActD诱导的细胞凋亡。AtILP N-末端结构域在植物中观察到的抗凋亡活性在动物系统中再现。过表达AtILP的转基因拟南芥品系在用真菌毒素伏马菌素B1（一种诱导植物中类似细胞死亡的药剂）挑战时表现出抗凋亡活性。在AtIPL转基因植物中，细胞死亡的抑制伴随着半胱天冬酶激活和DNA片段化的抑制。AtILP的过表达也减弱了效应蛋白诱导的细胞死亡，并增加了无毒细菌病原体的生长。目前的结果表明，存在一种新的植物IAP样蛋白，防止半胱天冬酶激活拟南芥，并表明，植物抗凋亡基因功能相似，在植物和动物系统。
A novel Arabidopsis thaliana inhibitor of apoptosis was identified by sequence homology to other known inhibitor of apoptosis (IAP) proteins. Arabidopsis IAP-like protein (AtILP) contained a C-terminal RING finger domain but lacked a baculovirus IAP repeat (BIR) domain, which is essential for antiapoptotic activity in other IAP family members. The expression of AtILP in HeLa cells conferred resistance against tumor necrosis factor (TNF)-alpha/ActD-induced apoptosis through the inactivation of caspase activity. In contrast to the C-terminal RING domain of AtILP, which did not inhibit the activity of caspase-3, the N-terminal region, despite displaying no homology to known BIR domains, potently inhibited the activity of caspase-3 in vitro and blocked TNF-alpha/ActD-induced apoptosis. The antiapoptotic activity of the AtILP N-terminal domain observed in plants was reproduced in an animal system. Transgenic Arabidopsis lines overexpressing AtILP exhibited anti-apoptotic activity when challenged with the fungal toxin fumonisin B1, an agent that induces apoptosis-like cell death in plants. In AtIPL transgenic plants, suppression of cell death was accompanied by inhibition of caspase activation and DNA fragmentation. Overexpression of AtILP also attenuated effector protein-induced cell death and increased the growth of an avirulent bacterial pathogen. The current results demonstrated the existence of a novel plant IAP-like protein that prevents caspase activation in Arabidopsis and showed that a plant anti-apoptosis gene functions similarly in plant and animal systems.