Glycosylation modulates TRAIL-R1/death receptor 4 protein: different regulations of two pro-apoptotic receptors for TRAIL by tunicamycin.
Glycosylation modulates TRAIL-R1/death receptor 4 protein: different regulations of two pro-apoptotic receptors for TRAIL by tunicamycin.
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DOI：
10.3892/or.18.5.1239
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发表时间：
2007-11
期刊：
影响因子：
4.2
通讯作者：
Tatsushi Yoshida;T. Shiraishi;Mano Horinaka;Miki Wakada;T. Sakai
中科院分区：
文献类型：
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作者：
Tatsushi Yoshida;T. Shiraishi;Mano Horinaka;Miki Wakada;T. Sakai
死亡受体4 （Death receptor 4, DR4）是抗肿瘤死亡配体、tnf相关凋亡诱导配体（TNF-related apoptosis-inducing ligand， TRAIL）的受体，被认为是一种很有前景的肿瘤治疗分子靶点。在这里，我们展示了一种新的DR4蛋白调控。Tunicamycin是一种内质网（ER）应激诱导剂，在前列腺癌DU145和PC3细胞中产生较低的DR4分子量模式，而不是DR5蛋白。因此，我们将DR4蛋白的小形式命名为DR4- small (DR4- s)，将大形式命名为DR4- large （DR4- l）。利用DR4 siRNA，我们证实DR4- s也代表DR4蛋白。其他er应激诱导剂brefeldin A和thapsigargin不产生DR4-S。另一方面，这些er胁迫诱导剂增加了DR5蛋白。Tunicamycin通过抑制n -链糖基化诱导内质网应激。因此，我们在糖基酶处理的细胞裂解物中检测了DR4蛋白。糖基酶处理产生DR4-S蛋白，类似于tunicamycin。这些结果表明，tunicamycin通过抑制糖基化调节DR4蛋白的大小。
Death receptor 4 (DR4) is a receptor of the antitumor death ligand, TNF-related apoptosis-inducing ligand (TRAIL), and is considered a promising molecular target for cancer therapy. Here, we show a novel regulation of DR4 protein. Tunicamycin treatment, which is an inducer of endoplasmic reticulum (ER)-stress, generated a lower molecular-weight pattern of DR4, but not DR5 protein in prostate cancer DU145 and PC3 cells. Thus, we termed the small form of DR4 protein, DR4-Small (DR4-S) and the large form, DR4-Large (DR4-L). Using DR4 siRNA, we confirmed that DR4-S also stands for DR4 protein. Other ER-stress inducers, brefeldin A and thapsigargin did not generate DR4-S. On the other hand, these ER-stress inducers increased DR5 protein. Tunicamycin induces ER-stress following the inhibition of N-linked glycosylation. Thus, we examined DR4 protein in cell lysates treated with glycosydase. Glycosydase treatments generated DR4-S protein, similar to tunicamycin. These results indicate that tunicamycin regulates DR4 protein size via inhibition of glycosylation.