Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals
Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals
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泛素连接酶 Cbl-b 通过激活线粒体途径并调节 Akt 和 ERK 生存信号使白血病和胃癌细胞对蒽环类药物敏感
DOI：
10.1016/j.febslet.2009.05.054
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发表时间：
2009-07-07
期刊：
影响因子：
3.5
通讯作者：
Liu, Yunpeng
中科院分区：
文献类型：
--
作者：
Qu, Xiujuan;Zhang, Ye;Liu, Yunpeng
本研究报道了蒽环类药物诱导RBL-2 H3白血病细胞和MGC 803胃癌细胞凋亡过程中泛素连接酶Cbl-b的表达上调。Cbl-b的过表达强烈地促进了蒽环类药物的细胞毒性和细胞毒性诱导作用，而显性阴性（DN）Cbl-b突变在两种细胞系中消除了这些作用。进一步的研究表明，在RBL-2 H3细胞中，Cbl-b增强线粒体去极化，而Cbl-b（DN）降低线粒体去极化。此外，Cbl-b的过表达显著抑制ERK激活，并且Cbl-b（DN）强烈增强ERK和Akt激活。总之，这些结果表明Cbl-b通过激活线粒体凋亡途径和调节ERK和Akt存活途径使白血病和胃癌细胞对蒽环类药物敏感。(C)2009年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
The present study reported that the ubiquitin ligase Cbl-b was up-regulated during anthracycline-induced apoptosis in two cell lines, RBL-2H3 leukemia cells and MGC803 gastric cancer cells. Overexpression of Cbl-b strongly promoted the cytotoxic and apoptosis-inducing effects of anthracyclines, while a dominant negative (DN) Cbl-b mutation abolished these effects in both cell lines. Further investigation revealed that mitochondrial depolarization was enhanced by Cbl-b and decreased by Cbl-b (DN) in RBL-2H3 cells. Moreover, overexpression of Cbl-b significantly suppressed ERK activation, and Cbl-b (DN) strongly enhanced both ERK and Akt activation. Altogether, these results indicate that Cbl-b sensitized both leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial apoptotic pathway and modulating the ERK and Akt survival pathways. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.