...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Involvement of Crm1 in Hepatitis B Virus X Protein-Induced Aberrant Centriole Replication and Abnormal Mitotic Spindles
【24h】

Involvement of Crm1 in Hepatitis B Virus X Protein-Induced Aberrant Centriole Replication and Abnormal Mitotic Spindles

机译：Crm1参与乙型肝炎病毒X蛋白诱导的异常离心复制和有丝分裂纺锤体异常。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Hepatitis B virus (HBV) includes an X gene (HBx gene) that plays a critical role in liver carcinogenesis. Because centrosome abnormalities are associated with genomic instability in most human cancer cells, we examined the effect of HBx on centrosomes. We found that HBx induced supernumerary centrosomes and multipolar spindles. This effect was independent of mutations in the p21 gene. Furthermore, the ability of HBV to induce supernumerary centrosomes was dependent on the presence of physiological HBx expression. We recently showed that HBx induces cytoplasmic sequestration of Crm1, a nuclear export receptor that binds to Ran GTPase, thereby inducing nuclear localization of NF-κB. Consistently, supernumerary centrosomes were observed in cells treated with a Crm1-specific inhibitor but not with an HBx mutant that lacked the ability to sequester Crm1 in the cytoplasm. Moreover, a fraction of Crm1 was found to be localized at the centrosomes. Immunocytochemical and ultrastructural examination of these supernumerary centrosomes revealed that inactivation of Crm1 was associated with abnormal centrioles. The presence of more than two centrosomes led to an increased frequency of defective mitoses and chromosome transmission errors. Based on this evidence, we suggest that Crm1 is actively involved in maintaining centrosome integrity and that HBx disrupts this process by inactivating Crm1 and thus contributes to HBV-mediated carcinogenesis.
机译：乙型肝炎病毒（HBV）包括在肝癌发生过程中起关键作用的X基因（HBx基因）。因为在大多数人类癌细胞中，中心体异常与基因组不稳定相关，所以我们检查了HBx对中心体的影响。我们发现HBx诱导了多余的中心体和多极纺锤体。这种作用与p21基因的突变无关。此外，HBV诱导多余的中心体的能力取决于生理性HBx表达的存在。我们最近发现HBx诱导Crm1的胞质隔离，Crm1是与Ran GTPase结合的核输出受体，从而诱导NF-κB的核定位。一致地，在用Crm1特异性抑制剂处理过的细胞中观察到多余的中心体，而在缺乏将Crm1隔离在细胞质中的能力的HBx突变体中则观察不到。此外，发现一部分Crm1位于中心体。这些多余的中心体的免疫细胞化学和超微结构检查表明，Crm1的失活与异常的中心体有关。超过两个中心体的存在导致有缺陷的有丝分裂频率增加和染色体传递错误。基于此证据，我们建议Crm1积极参与维持中心体完整性，并且HBx通过使Crm1失活而破坏了这一过程，从而促进了HBV介导的癌变。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号