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首页> 外文期刊>Life sciences >Novel transcript variants of TRAIL show different activities in activation of NF-kappaB and apoptosis.
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Novel transcript variants of TRAIL show different activities in activation of NF-kappaB and apoptosis.

机译：TRAIL的新型转录物变体在激活NF-κB和凋亡方面表现出不同的活性。

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AIMS: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has many transcript variants, but whether they possess distinct function is not completely known. In the present study, we compared the function of these TRAIL variants. MAIN METHODS: A bioinformatics analysis was performed to examine potential TRAIL variants. For the functional study, over-expression of TRAIL isoforms was used to examine their NF-kappaB inducing and apoptotic activities in both cancer and normal cells. Moreover, soluble TRAIL E4 variant protein was expressed and purified in prokaryotic cells, and was used for apoptotic assay. KEY FINDINGS: We cloned seven truncated TRAIL variants, designated as AK, E2, E3, E4, DA, BX424, and BX439. In comparison with the wild type TRAIL protein expressed from full-length RefSeq, over-expression of all these TRAIL variants activated NF-kappaB and its targeting genes in human cells at varying degrees. Some isoforms including BX424, DA and E4 even showed NF-kappaB, IL8, CCL4 and CCL20 promoter activating activity stronger than the wild type protein. All truncated variant proteins had no toxicity to normal human cells, similar to the wild type protein; however, they all failed to induce apoptosis in cancer cells that are sensitive to TRAIL. Recombinant soluble TRAIL E4 protein also failed to antagonize TRAIL-induced apoptosis in cancer cells. SIGNIFICANCE: Truncated TRAIL variant proteins lost apoptotic activity but retained or even enhanced the NF-kappaB activating potentials, these results suggest that TRAIL variants may play roles in non-apoptotic cellular processes that are more important than we previously thought.
机译：目的：肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）有许多转录变体，但它们是否具有独特的功能尚不完全清楚。在本研究中，我们比较了这些TRAIL变体的功能。主要方法：进行了生物信息学分析以检查潜在的TRAIL变体。对于功能研究，TRAIL亚型的过表达用于检查其在癌细胞和正常细胞中的NF-κB诱导和凋亡活性。此外，可溶性TRAIL E4变体蛋白在原核细胞中表达和纯化，并用于凋亡分析。主要发现：我们克隆了七个截短的TRAIL变体，分别命名为AK，E2，E3，E4，DA，BX424和BX439。与从全长RefSeq表达的野生型TRAIL蛋白相比，所有这些TRAIL变体的过量表达均在人体细胞中不同程度地激活了NF-κB及其靶向基因。包括BX424，DA和E4在内的一些同工型甚至显示出比野生型蛋白更强的NF-κB，IL8，CCL4和CCL20启动子激活活性。与野生型蛋白类似，所有截短的变体蛋白对正常人细胞均无毒性。然而，它们都未能诱导对TRAIL敏感的癌细胞凋亡。重组可溶性TRAIL E4蛋白也不能拮抗TRAIL诱导的癌细胞凋亡。意义：截短的TRAIL变体蛋白丧失了凋亡活性，但保留甚至增强了NF-κB的活化潜能，这些结果表明TRAIL变体可能在非凋亡细胞过程中发挥了重要作用，这一过程比我们以前认为的更为重要。

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