Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes
Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes
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DOI：
10.1038/379349a0
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发表时间：
1996-01-25
期刊：
影响因子：
64.8
通讯作者：
Korneluk, RG
中科院分区：
文献类型：
--
作者：
Liston, P;Roy, N;Korneluk, RG
细胞凋亡的调节异常可导致细胞死亡的不适当抑制，如发生在某些癌症的发展中（1），或无法控制细胞死亡的程度，如认为发生在获得性免疫缺陷和某些神经退行性疾病中，如脊髓性肌萎缩症（SMA）。最近，我们分离出一个SMA的候选基因，编码神经元凋亡抑制蛋白（NAIP）（2）。该基因与两种杆状病毒凋亡抑制蛋白同源（3，4）还报道了编码存活运动神经元（SMN）的第二种SMA候选基因，其与5q13.1上的NAIP基因座相邻（5）。在此，我们证明了NAIP介导的对由多种信号诱导的细胞凋亡的抑制，并鉴定了另外三个与杆状病毒IAP同源的人互补DNA和一个果蝇（Drosophilamelanogaster）序列。这四个开放阅读框（ORF）具有三个杆状病毒抑制凋亡蛋白重复（BIR）结构域和一个羧基末端RING锌指。人iap基因在胎儿和成人组织中有不同但重叠的表达模式。这些蛋白质显著增加已知凋亡抑制因子的数量。
DYSREGULATION Of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers(1), or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA). Recently, we isolated a candidate gene, encoding neuronal apoptosis inhibitor protein (NAIP)(2), for SMA. This gene is homologous to two baculovirus inhibitor of apoptosis proteins(3,4) (Cp-IAP and Op-IAP) and is partly deleted in individuals with type I SMA, A second SMA candidate gene encoding survival motor neuron (SMN), which is contiguous with the NAIP locus on 5q13.1, was also reported(5), Here we demonstrate a NAIP-mediated inhibition of apoptosis induced by a variety of signals, and have identified three additional human complementary DNAs and a Drosophila melanogaster sequence that are also homologous to the baculovirus IAPs, The four open reading frames (ORFs) possess three baculoviral inhibition of apoptosis protein repeat (BIR) domains and a carboxy-terminal RING zinc-finger. The human iap genes have a distinct but overlapping pattern of expression in fetal and adult tissues. These proteins significantly increase the number of known apoptotic suppressors.