Chicheportiche Y, Bourdon P R, Xu H, Hsu Y M, Scott H, Hession C, Garcia I, Browning J L
Department of Pathology, University of Geneva, 1211 Geneva 4, Switzerland.
J Biol Chem. 1997 Dec 19;272(51):32401-10. doi: 10.1074/jbc.272.51.32401.
The members of the tumor necrosis factor (TNF) family play pivotal roles in the regulation of the immune system. Here we describe a new ligand in this family, designated TWEAK. The mouse and human versions of this protein are unusually conserved with 93% amino acid identity in the receptor binding domain. The protein was efficiently secreted from cells indicating that, like TNF, TWEAK may have the long range effects of a secreted cytokine. TWEAK transcripts were abundant and found in many tissues, suggesting that TWEAK and TRAIL belong to a new group of widely expressed ligands. Like many members of the TNF family, TWEAK was able to induce interleukin-8 synthesis in a number of cell lines. The human adenocarcinoma cell line, HT29, underwent apoptosis in the presence of both TWEAK and interferon-gamma. Thus, TWEAK resembles many other TNF ligands in the capacity to induce cell death; however, the fact that TWEAK-sensitive cells are relatively rare suggests that TWEAK along with lymphotoxins alpha/beta and possibly CD30L trigger death via a weaker, nondeath domain-dependent mechanism.
肿瘤坏死因子（TNF）家族成员在免疫系统调节中发挥关键作用。在此，我们描述该家族中的一种新配体，命名为TWEAK。这种蛋白质的小鼠和人类版本异常保守，在受体结合域中氨基酸同一性达93%。该蛋白质能从细胞中有效分泌，这表明，与TNF一样，TWEAK可能具有分泌型细胞因子的远距离作用。TWEAK转录本丰富，在许多组织中都能找到，这表明TWEAK和TRAIL属于一组新的广泛表达的配体。与TNF家族的许多成员一样，TWEAK能够在多种细胞系中诱导白细胞介素-8的合成。人腺癌细胞系HT29在TWEAK和干扰素-γ共同存在的情况下发生凋亡。因此，TWEAK在诱导细胞死亡的能力方面类似于许多其他TNF配体；然而，对TWEAK敏感的细胞相对较少这一事实表明，TWEAK与淋巴毒素α/β以及可能的CD30L通过一种较弱的、非死亡结构域依赖性机制触发细胞死亡。
