Deterin, a new inhibitor of apoptosis from Drosophila melanogaster
Deterin, a new inhibitor of apoptosis from Drosophila melanogaster
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DOI：
10.1074/jbc.m000369200
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发表时间：
2000-07-21
影响因子：
4.8
通讯作者：
Chu, YX
中科院分区：
文献类型：
--
作者：
Jones, G;Jones, D;Chu, YX
Deterin是一种来自黑腹果蝇的新的细胞凋亡抑制因子，它具有一个独特的结构，只有一个杆状病毒的凋亡抑制因子(LAP)类型的重复序列，没有环指基序。在SF9和S2细胞的转染实验中，Definin的生化作用被证明，其中表达的蛋白作用于细胞质中，以抑制或阻止细胞凋亡，否则由caspase依赖的凋亡激活剂或细胞毒物诱导，细胞死亡决定蛋白的功能表型的丧失通过与显性负定抗素突变体或DIAP1或p35的抑制性RNA(RNAi)的转染来指示，DIAP1或p35的抗凋亡活性不受抑制。杆状病毒IAP型重复(BIR)结构域和α-螺旋C末端结构域在SF9和52细胞中都是必需的，以显示其防止细胞死亡的活性。在胚胎、三龄幼虫、成年雌性幼虫的酸性晚期哺育细胞中存在大约650个碱基的defiin转录本。抑制素转录本分布在早期胚胎中，而在晚期胚胎中，它逐渐局限于中枢神经系统和性腺。然而到目前为止，线虫Survivin-type ZAP仅被认为是有丝分裂调节因子，而果蝇Definin构成了Sunvivin-type IAP组中第一个表现出凋亡抑制活性的无脊椎动物成员。
Deterin, a new apoptosis inhibitor from Drosophila melanogaster, possesses an unusual structure of only a single baculovirus inhibitor of apoptosis (LAP)-type repeat and no RING finger motif. The biochemical actions of deterin are demonstrated in SF9 and S2 cell transfection assays, in which the expressed protein acts in the cytoplasm to inhibit or deter cells from apoptosis otherwise induced by the caspase-dependent apoptosis activator reaper or by cytotoxicants, A loss of function phenotype for deterin of cell death was indicated by transfections with either a dominant negative deterin mutant or with inhibitory RNA (RNAi) for deterin, The dominant negative C-terminal fragment that antagonized antiapoptotic activity of deterin did not affect antiapoptotic activity of DIAP1 or p35. Both the baculovirus IAP-type repeat (BIR) domain and the alpha-helical C-terminal domain are necessary in both SF9 and 52 cells for deterin to manifest its activity to prevent cell death. The approximately 650-base deterin transcript is present in embryos, third instar larvae, acid late stage nurse cells of adult females. The deterin transcript is distributed throughout early stage embryos, whereas in later stage embryos it becomes progressively restricted to the central nervous system and gonads. Whereas the nematode survivin-type ZAP has thus far been implicated only as a mitotic regulator, Drosophila deterin constitutes the first invertebrate member of the sunvivin-type IAP group to exhibit apoptosis-inhibitory activity.