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Oncol Rep. 2007 Nov;18(5):1239-42.

Glycosylation modulates TRAIL-R1/death receptor 4 protein: different regulations of two pro-apoptotic receptors for TRAIL by tunicamycin.

Author information

1
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

Abstract

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.

PMID:
17914579
[Indexed for MEDLINE]

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