Activation of protein phosphatase causes alternative splicing of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): Potential effect on immune surveillance
Activation of protein phosphatase causes alternative splicing of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): Potential effect on immune surveillance
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DOI：
10.1016/j.bbrc.2007.06.046
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发表时间：
2007-08-17
影响因子：
3.1
通讯作者：
Eguchi, Katsumi
中科院分区：
文献类型：
--
作者：
Kamachi, Makoto;Aramaki, Toshiyuki;Eguchi, Katsumi
肿瘤坏死因子相关凋亡诱导配体（TRAIL）属于TNF超家族蛋白质。它在刺激后在自然杀伤细胞、细胞毒性T淋巴细胞和单核细胞上高度表达，并在免疫监视中起关键作用。最近鉴定了两种TRAIL剪接变体，它们没有促凋亡活性。剪接因子中的磷酸化水平，富含丝氨酸-精氨酸（SR）和异质性核糖核蛋白（hnRNP）控制着几个糖尿病相关基因的mRNA剪接。我们描述了凋亡刺激介导的TRAIL选择性剪接模式，并研究了选择性剪接的可能机制。依托泊苷和放线菌酮诱导选择性剪接，而星形孢菌素（一种广泛的激酶抑制剂）阻断组成性和选择性剪接。从头神经酰胺合成和随后的蛋白磷酸酶-1（PP-1）激活增强了选择性剪接，TNF-α刺激也是如此，但干扰素α（IFN-α）刺激则不然。我们证明，TRAIL通过mRNA剪接改变基因表达，并可能改变细胞因子刺激的促凋亡潜力。(c)2007年爱思唯尔公司All rights reserved.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) belongs to the TNF superfamily of proteins. It is highly expressed on natural killer cells, cytotoxic T lymphocytes, and monocytes after stimulation, and plays a critical role in immune surveillance. Two splice variants of TRAIL were identified recently that show no proapoptotic activity. Phosphorylation level in splicing factors, serine-arginine-rich (SR) and heterogeneous ribonucleoproteins (hnRNPs) govern the mRNA splicing of several apoptosis-related genes. We characterized the apoptotic stimuli-mediated alternative splicing pattern of TRAIL and investigated the possible underlying mechanism of alternative splicing. Etoposide and cycloheximide induced alternative splicing, whereas staurosporine (a broad kinase inhibitor) blocked both constitutive and alternative splicing. De novo ceramide synthesis and subsequent protein phosphatase-1 (PP-1) activation enhanced the alternative splicing, as did TNF-alpha but not interferon alpha (IFN-alpha) stimulation. We demonstrated that TRAIL alters gene expression through mRNA splicing and may change proapoptotic potential in response to cytokine stimulation. (c) 2007 Elsevier Inc. All rights reserved.