...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Deletion of either C-terminal transactivation subdomain enhances the in vitro transforming activity of human transcription factor REL in chicken spleen cells
【24h】

Deletion of either C-terminal transactivation subdomain enhances the in vitro transforming activity of human transcription factor REL in chicken spleen cells

机译：删除任何一个C末端反式激活亚结构域可增强人转录因子REL在鸡脾细胞中的体外转化活性

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

摘要

The REL gene is amplified in many human B-cell lymphomas and we have previously shown that expression of REL from a retroviral vector can malignantly transform chicken spleen cells in vitro. To identify REL protein functions necessary for malignant transformation, we have performed deletion analysis on REL sequences encoding residues of two C-terminal subdomains that are involved in transcriptional activation. We find that deletion of both C-terminal transactivation subdomains abolishes the ability of REL to transform chicken spleen cells in vitro. In contrast, deletion of either transactivation subdomain alone, which reduces the transactivation ability of REL, enhances the transforming activity of REL. Transforming REL mutants missing C-terminal sequences can also be selected at a low frequency in vitro. The REL transactivation domain can be functionally replaced in transformation assays by a portion of the VP16 transactivation domain that activates at a level similar to REL-transforming mutants. We also find that deletion of 29 C-terminal amino acids causes the subcellular localization of REL to change from cytoplasmic to nuclear in chicken embryo fibroblasts. In contrast, wild-type REL and all transforming REL mutants are located primarily in the cytoplasm of transformed spleen cells. Nevertheless, treatment of transformed spleen cells with leptomycin B causes wild-type REL and two REL mutants to relocalize to the nucleus, and nuclear extracts from these transformed cells contain REL DNA-binding activity. Taken together, these results suggest the following: (1) that REL must activate transcription to transform cells in vitro; (2) that a reduced level of transactivation enhances the oncogenicity of REL; (3) that REL shuttles from the cytoplasm to the nucleus in transformed chicken spleen cells; and (4) that mutations in REL, in addition to amplifications, could activate its oncogenicity in human lymphomas.
机译：REL基因在许多人类B细胞淋巴瘤中都有扩增，我们以前已经证明逆转录病毒载体中REL的表达可以在体外恶性转化鸡脾细胞。为了确定恶性转化所必需的REL蛋白功能，我们对编码两个参与转录激活的C末端亚结构域残基的REL序列进行了缺失分析。我们发现，删除两个C末端反式激活子域都消除了REL在体外转化鸡脾细胞的能力。相反，单独缺失任一反式激活子域会降低REL的反式激活能力，从而增强REL的转化活性。也可以在体外以低频选择缺少C末端序列的转化REL突变体。 REL反式激活结构域可以在转化测定中被VP16反式激活结构域的一部分功能性地替代，该VP16反式激活结构域的激活水平类似于REL-转化突变体。我们还发现删除29个C末端氨基酸会导致REL的亚细胞定位在鸡胚成纤维细胞中从胞质变为核。相反，野生型REL和所有转化REL突变体主要位于转化的脾细胞的细胞质中。然而，用瘦霉素B处理转化的脾细胞导致野生型REL和两个REL突变体重新定位到核，并且来自这些转化细胞的核提取物具有REL DNA结合活性。综上所述，这些结果表明：（1）REL必须激活转录才能在体外转化细胞; （2）减少的反式激活可增强REL的致癌性; （3）REL在转化的鸡脾细胞中从细胞质穿梭到细胞核; （4）REL中的突变除了扩增外，还可以激活其在人类淋巴瘤中的致癌性。

著录项

相似文献

  • 外文文献
  • 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