Identification of a novel gene family, paralogs of inhibitor of apoptosis proteins present in plants, fungi, and animals

Identification of a novel gene family, paralogs of inhibitor of apoptosis proteins present in plants, fungi, and animals
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DOI:
10.1007/s10495-005-1876-1
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发表时间:
2005-05-01
期刊:
影响因子:
7.2
通讯作者:
Kuchitsu, K
Kuchitsu, K
中科院分区:
生物学2区
文献类型:
--
作者:
Higashi, K;Takasawa, R;Kuchitsu, K

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在植物中发现的动物细胞凋亡调节因子的直系同源物很少。最近,哺乳动物细胞凋亡抑制蛋白(IAP)的异位表达已被证明影响植物细胞程序性死亡。在这里,我们通过应用改进的基序搜索方法鉴定了两个与拟南芥IAP样蛋白(AtILP)1和2同源的新蛋白。此外,AtILP 1的同源物被发现作为一个新的基因家族出现在其他生物体,如真菌和动物,包括智人(HsILP 1)。与IAP中的杆状病毒IAP重复序列(BIRs)一样,ILP含有两个高度保守的BIR-like结构域(BLDs),具有推定的C2 HC型锌指。系统发育分析表明ILP是IAP的旁系同源物。同源模建显示HsILP 1中BLD的三维结构与BIR的三维结构相似。瞬时表达HsILP 1可抑制足叶乙甙诱导的HEK 293和HeLaS 3细胞凋亡。这些发现表明ILP在包括植物在内的广泛的真核生物中是保守的,并且它们的功能与IAP的功能密切相关。
Only few orthologs of animal apoptosis regulators have been found in plants. Recently, the ectopic expression of mammalian inhibitor of apoptosis proteins (IAPs) has been shown to affect plant programmed cell death. Here, we identified two novel proteins homologous to Arabidopsis thaliana IAP-like protein (AtILP) 1 and 2 by applying an improved motif searching method. Furthermore, homologs of AtILP1 were found to occur as a novel gene family in other organisms such as fungi and animals including Homo sapiens (HsILP1). Like baculovirus IAP repeats (BIRs) in IAPs, ILPs contain two highly conserved BIR-like domains (BLDs) with a putative C2HC-type zinc finger. Phylogenetic analyses indicated that ILPs are putative paralogs of IAPs. Homology modeling revealed that the three-dimensional structure of BLD in HsILP1 is similar to that of BIR. Transient expression of HsILP1 resulted in inhibition of etoposide-induced apoptosis in HEK293 and HeLaS3 cells. These findings suggest that ILPs are conserved in a wide range of eukaryotes including plants, and that their functions are closely related to those of IAPs.