Emery J G, McDonnell P, Burke M B, Deen K C, Lyn S, Silverman C, Dul E, Appelbaum E R, Eichman C, DiPrinzio R, Dodds R A, James I E, Rosenberg M, Lee J C, Young P R
Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA.
J Biol Chem. 1998 Jun 5;273(23):14363-7. doi: 10.1074/jbc.273.23.14363.
TRAIL is a tumor necrosis factor-related ligand that induces apoptosis upon binding to its death domain-containing receptors, DR4 and DR5. Two additional TRAIL receptors, TRID/DcR1 and DcR2, lack functional death domains and function as decoy receptors for TRAIL. We have identified a fifth TRAIL receptor, namely osteoprotegerin (OPG), a secreted tumor necrosis factor receptor homologue that inhibits osteoclastogenesis and increases bone density in vivo. OPG-Fc binds TRAIL with an affinity of 3.0 nM, which is slightly weaker than the interaction of TRID-Fc or DR5-Fc with TRAIL. OPG inhibits TRAIL-induced apoptosis of Jurkat cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These data suggest potential cross-regulatory mechanisms by OPG and TRAIL.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种肿瘤坏死因子相关配体，与含死亡结构域的受体DR4和DR5结合后可诱导细胞凋亡。另外两种TRAIL受体，即TRID/DcR1和DcR2，缺乏功能性死亡结构域，可作为TRAIL的诱饵受体发挥作用。我们鉴定出了第五种TRAIL受体，即骨保护素（OPG），它是一种分泌型肿瘤坏死因子受体同源物，在体内可抑制破骨细胞生成并增加骨密度。OPG-Fc以3.0 nM的亲和力结合TRAIL，这略弱于TRID-Fc或DR5-Fc与TRAIL的相互作用。OPG可抑制TRAIL诱导的Jurkat细胞凋亡。相反，TRAIL可阻断OPG的抗破骨细胞生成活性。这些数据提示了OPG和TRAIL之间潜在的交叉调节机制。
