Pradet-Balade B, Medema J P, López-Fraga M, Lozano J C, Kolfschoten G M, Picard A, Martínez-A C, Garcia-Sanz J A, Hahne M
Department of Immunology and Oncology, Centro Nacional de Biotecnología, E-28049 Madrid, Spain.
EMBO J. 2002 Nov 1;21(21):5711-20. doi: 10.1093/emboj/cdf565.
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.
TWEAK和APRIL是最近发现的肿瘤坏死因子（TNF）配体家族成员，分别与血管生成和免疫调节有关。TWEAK是一种在细胞表面表达的跨膜蛋白，而APRIL仅作为一种分泌因子发挥作用。在本报告中，我们利用RACE、RT-PCR、cDNA文库筛选和核糖核酸酶保护试验，对TWEAK和APRIL mRNA之间的一种杂交转录本进行了表征。编码的TWE-PRIL蛋白由与APRIL C末端结构域融合的TWEAK细胞质和跨膜结构域组成。TWE-PRIL mRNA在人原代T细胞和单核细胞中表达并翻译，并且在原代人T淋巴细胞和单核细胞系中检测到内源性TWE-PRIL蛋白。TWE-PRIL通过膜锚定，并在细胞表面呈现APRIL受体结合结构域。它是一种生物活性配体，因为它能刺激T和B淋巴瘤细胞系的细胞周期。与膜结合型和分泌型肿瘤坏死因子-α非常相似，TWE-PRIL和APRIL不同的细胞定位表明它们发挥着不同的生物学作用。
