Proteomic profiling revealed the functional networks associated with mitotic catastrophe of HepG2 hepatoma cells induced by 6-bromine-5-hydroxy-4-methoxybenzaldehyde
Proteomic profiling revealed the functional networks associated with mitotic catastrophe of HepG2 hepatoma cells induced by 6-bromine-5-hydroxy-4-methoxybenzaldehyde
复制标题
蛋白质组分析揭示了与 6-溴-5-羟基-4-甲氧基苯甲醛诱导的 HepG2 肝癌细胞有丝分裂灾难相关的功能网络
DOI：
10.1016/j.taap.2011.03.003
复制
发表时间：
2011-05-01
影响因子：
3.8
通讯作者：
Zhou, Ping-Kun
中科院分区：
文献类型：
--
作者：
Zhang, Bo;Huang, Bo;Zhou, Ping-Kun
有丝分裂突变是由异常有丝分裂引起的一种细胞死亡形式，是一种细胞毒性死亡途径，也是抗癌药物开发的一种诱人的机制策略。在本研究中，6-溴-5-羟基-4-甲氧基苯甲醛诱导人肝癌细胞系HepG2细胞DNA双链断裂、多极纺锤体、维持有丝分裂停滞和产生多核细胞，所有这些都表明是有丝分裂的灾难。我们使用蛋白质组学图谱来鉴定与有丝分裂灾难相关的差异表达的蛋白质。共鉴定出137个差异表达蛋白(76个上调蛋白和61个下调蛋白)。一些变化的蛋白质与有丝分裂灾难相关，如DNA-PKcs、FOXM1、RCC1、Cyclin E、PLK1-pT210、14-3-3sigma和HSP70。多种异构体14-3-3、热休克蛋白和微管蛋白表达上调。功能意义分析表明，14-3-3介导的信号网络对差异表达蛋白的丰度最高。这些调控蛋白参与了大分子复合体的组装、细胞死亡、细胞周期、染色质重塑和DNA修复、微管蛋白和细胞骨架的组织。这些发现揭示了与纺锤体破坏和有丝分裂灾难相关的整体分子事件和功能信号网络。(C)2011 Elsevier Inc.保留所有权利。
Mitotic catastrophe, a form of cell death resulting from abnormal mitosis, is a cytotoxic death pathway as well as an appealing mechanistic strategy for the development of anti-cancer drugs. In this study, 6-bromine-5-hydroxy-4-methoxybenzaldehyde was demonstrated to induce DNA double-strand break, multipolar spindles, sustain mitotic arrest and generate multinucleated cells, all of which indicate mitotic catastrophe, in human hepatoma HepG2 cells. We used proteomic profiling to identify the differentially expressed proteins underlying mitotic catastrophe. A total of 137 differentially expressed proteins (76 upregulated and 61 downregulated proteins) were identified. Some of the changed proteins have previously been associated with mitotic catastrophe, such as DNA-PKcs, FoxM1, RCC1, cyclin E, PLK1-pT210, 14-3-3 sigma and HSP70. Multiple isoforms of 14-3-3, heat-shock proteins and tubulin were upregulated. Analysis of functional significance revealed that the 14-3-3-mediated signaling network was the most significantly enriched for the differentially expressed proteins. The modulated proteins were found to be involved in macromolecule complex assembly, cell death, cell cycle, chromatin remodeling and DNA repair, tubulin and cytoskeletal organization. These findings revealed the overall molecular events and functional signaling networks associated with spindle disruption and mitotic catastrophe. (C) 2011 Elsevier Inc. All rights reserved.