Isoprenoid biosynthetic pathway inhibition disrupts monoclonal protein secretion and induces the unfolded protein response pathway in multiple myeloma cells
Isoprenoid biosynthetic pathway inhibition disrupts monoclonal protein secretion and induces the unfolded protein response pathway in multiple myeloma cells
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DOI：
10.1016/j.leukres.2010.08.008
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发表时间：
2011-04-01
影响因子：
2.7
通讯作者：
Hohl, Raymond J.
中科院分区：
文献类型：
--
作者：
Holstein, Sarah A.;Hohl, Raymond J.
骨髓瘤的特征是单克隆蛋白的过度产生和分泌。类异戊二烯生物合成途径（IBP）的抑制剂在骨髓瘤细胞中具有多效性。为了研究IBP抑制是否干扰单克隆蛋白分泌，用IBP或异戊二烯基转移酶的特异性抑制剂处理人骨髓瘤细胞。这些研究表明，抑制Rab香叶基香叶基化的试剂破坏轻链运输，导致轻链在内质网中积累，激活未折叠蛋白反应途径并诱导细胞凋亡。这些研究为IBP抑制剂提供了一种新的作用机制，并表明有必要进一步探索Rab-targeted药物在骨髓瘤中的作用。(c)2010爱思唯尔有限公司保留所有权利。
Myeloma is characterized by the overproduction and secretion of monoclonal protein. Inhibitors of the isoprenoid biosynthetic pathway (IBP) have pleiotropic effects in myeloma cells. To investigate whether IBP inhibition interferes with monoclonal protein secretion, human myeloma cells were treated with specific inhibitors of the IBP or prenyltransferases. These studies demonstrate that agents that inhibit Rab geranylgeranylation disrupt light chain trafficking, lead to accumulation of light chain in the endoplasmic reticulum, activate the unfolded protein response pathway and induce apoptosis. These studies provide a novel mechanism of action for IBP inhibitors and suggest that further exploration of Rab-targeted agents in myeloma is warranted. (c) 2010 Elsevier Ltd. All rights reserved.