An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein
An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein
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DOI：
10.1093/emboj/cdf565
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发表时间：
2002-11-01
期刊：
影响因子：
11.4
通讯作者：
Hahne, M
中科院分区：
文献类型：
--
作者：
Pradet-Balade, B;Medema, JP;Hahne, M
TWEAK和APRIL是最近发现的两个肿瘤坏死因子（TNF）配体家族成员，分别与血管生成和免疫调节有关。TWEAK是一种表达于细胞表面的跨膜蛋白，而APRIL仅作为一种分泌因子。在本报告中，我们利用RACE、RT-PCR、cDNA文库筛选和RNase保护实验，鉴定了TWEAK和APRIL mrna之间的杂交转录物。编码的twee - pril蛋白由融合到APRIL c端结构域的TWEAK细胞质和跨膜结构域组成。twee - pril mRNA在人原代T细胞和单核细胞中表达和翻译，在人原代T细胞和单核细胞系中检测到内源性twee - pril蛋白。TWE-PRIL是膜锚定的，在细胞表面呈现APRIL受体结合域。它是一种生物活性配体，因为它刺激T和b淋巴瘤细胞系的循环。就像膜结合和分泌的tnf - α一样，twee - pril和APRIL的不同细胞定位表明它们发挥着不同的生物学作用。
TWEAK and APRIL are two recently identified tumour necrosis factor (TNF) ligand family members, implicated in angiogenesis and immune regulation, respectively. TWEAK is a transmembrane protein expressed on the cell surface, whereas APRIL acts solely as a secreted factor. In this report, using RACE, RT-PCR, cDNA library screening and an RNase protection assay, we characterize a hybrid transcript between TWEAK and APRIL mRNAs. The encoded TWE-PRIL protein is composed of TWEAK cytoplasmic and transmembrane domains fused to the APRIL C-terminal domain. TWE-PRIL mRNA is expressed and translated in human primary T cells and monocytes, and endogenous TWE-PRIL protein was detected in primary human T lymphocytes and monocytic cell lines. TWE-PRIL is membrane anchored and presents the APRIL receptor-binding domain at the cell surface. It is a biologically active ligand, as it stimulates cycling in T- and B-lymphoma cell lines. Much like membrane-bound and secreted TNF-alpha, the different cellular localizations of TWE-PRIL and APRIL suggest that they exert distinct biological roles.