A novel 21-kDa cytochrome c-releasing factor is generated upon treatment of human leukemia U937 cells with geranylgeraniol

A novel 21-kDa cytochrome c-releasing factor is generated upon treatment of human leukemia U937 cells with geranylgeraniol
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DOI:
10.1016/j.bbrc.2006.05.161
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发表时间:
2006-07-28
影响因子:
3.1
通讯作者:
Nakaya, Kazuyasu
Nakaya, Kazuyasu
中科院分区:
生物学4区
文献类型:
--
作者:
Masuda, Yutaka;Maeda, Sayoko;Nakaya, Kazuyasu

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香叶基香叶醇(GGO)通过依赖于细胞因子的途径诱导多种人类肿瘤细胞系的凋亡。本研究描述了一个21 kDa的细胞色素c释放因子,出现在细胞质组分与GGO治疗后的人白血病U937细胞的鉴定。将分离的线粒体与用GGO处理过的U937细胞的裂解物一起孵育,导致细胞色素c从线粒体中释放。利用这种无细胞系统,我们纯化了一种21 kDa的蛋白质,该蛋白质诱导线粒体释放细胞色素e,并参与GGO诱导的U937细胞凋亡。我们将这种蛋白质命名为细胞色素C释放因子21(CRF21)。CRF21在HeLa细胞中的过表达诱导线粒体释放细胞色素c,随后发生凋亡。我们的研究结果表明,CRF21可能在GGO诱导白血病U937细胞凋亡中起重要作用。(c)2006年爱思唯尔公司All rights reserved.
Geranylgeraniol (GGO) induces apoptosis in various lines of human tumor cells through a mitochondrion-dependent pathway. The present study describes identification of a 21-kDa cytochrome c-releasing factor that appears in the cytosolic fraction after treatment of human leukemia U937 cells with GGO. Incubation of isolated mitochondria with a lysate of U937 cells that had been treated with GGO resulted in the release of cytochrome c from the mitochondria. Utilizing this cell-free system, we purified a 21-kDa protein that induced the release of cytochrome e from mitochondria and appeared to be involved in the apoptosis that is induced in U937 cells by GGO. We designated this protein cytochrome c-releasing factor 21 (CRF21). Overexpression of CRF21 in HeLa cells induced the release of cytochrome c from mitochondria, with subsequent apoptosis. Our results suggest that CRF21 might play an important role in the induction of apoptosis by GGO in leukemia U937 cells. (c) 2006 Elsevier Inc. All rights reserved.