...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Gamma Interferon and Cadmium Treatments Modulate Eukaryotic Initiation Factor 4E-Dependent mRNA Transport of Cyclin D1 in a PML-Dependent Manner
【24h】

Gamma Interferon and Cadmium Treatments Modulate Eukaryotic Initiation Factor 4E-Dependent mRNA Transport of Cyclin D1 in a PML-Dependent Manner

机译：γ干扰素和镉治疗以PML依赖性方式调节Cyclin D1的真核起始因子4E依赖性mRNA转运。

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

摘要

The eukaryotic initiation factor 4E (eIF4E), when dysregulated, transforms cells. A substantial fraction of eIF4E forms nuclear bodies that colocalize with those associated with the promyelocytic leukemia protein PML. Overexpression studies indicate that nuclear eIF4E promotes the transport of cyclin D1 mRNA from the nucleus to the cytoplasm and that PML is a key negative regulator of this function. Since previous studies used overexpression methods, the physiological relevance of eIF4E mRNA transport function or its interaction with PML remained unknown. Therefore, we monitored whether eIF4E-dependent transport could be modulated in response to environmental conditions. Here we report that cadmium treatment, which disperses PML nuclear bodies, leaves eIF4E bodies intact, leading to increased transport of cyclin D1 mRNA and increased cyclin D1 protein levels. Removal of cadmium allows PML to reassociate with eIF4E nuclear bodies, leading to decreased cyclin D1 transport and reduced cyclin D1 protein levels. In contrast, we show that treating cells with interferon increased the levels of PML protein at the PML-eIF4E nuclear body, leading to nuclear retention of cyclin D1 transcripts and reduced cyclin D1 protein levels. Neither interferon nor cadmium treatment altered cyclin D1 levels in PML?/? cells. Consistently, overexpression of a series of PML and eIF4E mutant proteins established that PML eIF4E interaction is required for the observed effects of cadmium and interferon treatment. The present study provides the first evidence that physiological factors modulate the mRNA transport functions of eIF4E and that this regulation is PML dependent.
机译：失调的真核起始因子4E（eIF4E）转化细胞。 eIF4E的很大一部分形成了与早幼粒细胞白血病蛋白PML相关的核体。过度表达研究表明，核eIF4E促进细胞周期蛋白D1 mRNA从细胞核到细胞质的转运，而PML是此功能的关键负调控因子。由于先前的研究使用过表达方法，因此eIF4E mRNA转运功能或其与PML相互作用的生理相关性仍然未知。因此，我们监测了是否可以响应环境条件来调节依赖eIF4E的运输。在这里，我们报告称，镉处理可分散PML核小体，使eIF4E小体完好无损，从而导致细胞周期蛋白D1 mRNA的运输增加和细胞周期蛋白D1蛋白的水平增加。去除镉可使PML与eIF4E核体重新结合，从而导致细胞周期蛋白D1转运减少和细胞周期蛋白D1蛋白水平降低。相反，我们表明用干扰素处理细胞会增加PML-eIF4E核体中PML蛋白的水平，从而导致细胞周期蛋白D1转录本的核保留并降低细胞周期蛋白D1的蛋白水平。干扰素和镉处理均未改变PML ？/？细胞中细胞周期蛋白D1的水平。一致地，一系列PML和eIF4E突变蛋白的过表达确定了PML eIF4E相互作用对于观察到的镉和干扰素治疗的作用是必需的。本研究提供了第一个证据，即生理因素调节eIF4E的mRNA转运功能，并且该调节是PML依赖性的。

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