The NB-ARC domain: a novel signalling motif shared by plant resistance gene products and regulators of cell death in animals
The NB-ARC domain: a novel signalling motif shared by plant resistance gene products and regulators of cell death in animals
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DOI：
10.1016/s0960-9822(98)70145-9
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发表时间：
1998-03
期刊：
影响因子：
9.2
通讯作者：
E. A. Biezen;Jonathan D. G. Jones
中科院分区：
文献类型：
--
作者：
E. A. Biezen;Jonathan D. G. Jones
细胞程序性死亡在植物和动物的发育中起着重要的作用[1，2]。细胞外死亡诱导刺激通常导致动物细胞中半胱氨酸蛋白酶的激活：半胱天冬酶[3]。许多底物的蛋白水解裂解然后导致独特的形态学特征，如细胞质的浓缩和DNA片段化。半胱天冬酶活性在秀丽隐杆线虫中由细胞死亡基因ced-9和ced-4调节[1]。ced-9基因及其哺乳动物同源物Bcl-2家族编码保护细胞免于死亡的负调节因子。ced-4基因和最近鉴定的人类同源物Apaf-1 [4]编码ced-9/Bcl-2死亡防御者和半胱天冬酶杀伤者之间的控制衔接子（在C.有趣的是，数据库搜索与CED-4 [5]和APAF-1具有同源性的蛋白质鉴定了几种植物抗性（R）基因产物。在GenBank数据库的BLAST-P搜索[6]中使用包含APAF-1 [4]的氨基酸92-412的区域，显示几种R基因产物具有与CED-4相当的同源性（约50%相似性）。该区域包括一个核苷酸结合（NB）结构域，由激酶1a（P环）、2和3a基序[7]以及其他几个功能未知的短保守基序组成（图1）。R基因产物在结构上也与CED-4和APAF-1相似（图2），具有氨基末端效应结构域和羧基末端富含亮氨酸的重复序列（LRR），与APAF-1中的WD-40重复序列一样[4]，通常参与蛋白质-蛋白质相互作用[8]。
Programmed cell death plays an important role in plant and animal development [1, 2]. Extracellular death-inducing stimuli often lead in animal cells to the activation of cysteine proteases: the caspases [3]. Proteolytic cleavage of a number of substrates then results in distinctive morphological features, such as condensation of cytoplasm and DNA fragmentation. Caspase activity is regulated in Caenorhabditis elegans by the cell death genes ced-9 and ced-4 [1]. The ced-9 gene and its mammalian homologues, the Bcl-2 family, encode negative regulators that protect cells from death. The ced-4 gene and the recently identified human homologue, Apaf-1 [4], encode controlling adaptors between the ced-9/Bcl-2 death defenders and the caspase killers (encoded in C. elegans by ced-3).Interestingly, database searches for proteins with homology to CED-4 [5] and APAF-1 identified several plant resistance (R) gene products. Using a region comprising amino acids 92–412 of APAF-1 [4] in a BLAST-P search [6] of the GenBank database, several R gene products were shown to have homology (∼ 50% similarity) comparable to that of CED-4. This region includes a nucleotide-binding (NB) domain, consisting of kinase 1a (P-loop), 2 and 3a motifs [7], and several other short conserved motifs with unknown function (Figure 1). The R gene products are also similar to CED-4 and APAF-1 structurally (Figure 2), with an amino-terminal effector domain and carboxy-terminal leucine-rich repeats (LRRs) that are, like the WD-40 repeats in APAF-1 [4], often involved in protein–protein interactions [8].