...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >C-Terminal Regions of the Human Telomerase Catalytic Subunit Essential for In Vivo Enzyme Activity
【24h】

C-Terminal Regions of the Human Telomerase Catalytic Subunit Essential for In Vivo Enzyme Activity

机译：体内酶活性必不可少的人类端粒酶催化亚基的C末端区域

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

摘要

Most human cancer cells are thought to acquire the ability to divide beyond the capacity of normal somatic cells through illegitimately activating the gene hTERT, which encodes the catalytic subunit of telomerase. While telomerase reverse transcriptase (TERT) is conserved in most eukaryotes, mounting evidence suggests that the C terminus of the human protein may have functions unique to higher eukaryotes. To search for domains responsible for such functions, we assayed a panel of tandem substitution mutations encompassing this region of human TERT for in vitro and in vivo functionality. We found four clusters of mutations that inactivated the biochemical and biological functions of telomerase, separated by mutations that had little or no effect on enzyme activity. We also identified a region where mutations generate catalytically active but biologically inert proteins. This C-terminal region that dissociates activities of telomerase (C-DAT) does not appear to be involved in nuclear localization or protein multimerization. Instead, it appears that the C-DAT region is involved in a step of in vivo telomere synthesis after the assembly of a catalytically active enzyme. Intriguingly, all of the described regions reside in a portion of TERT that is dispensable for cellular viability in yeast, arguing for a divergent role of the C terminus in higher eukaryotes.
机译：据认为，大多数人类癌细胞通过非法激活编码端粒酶催化亚基的基因“ hTERT”来获得超越正常体细胞分裂能力。虽然端粒酶逆转录酶（TERT）在大多数真核生物中都是保守的，但越来越多的证据表明，人类蛋白质的C末端可能具有高级真核生物所独有的功能。为了寻找负责这种功能的结构域，我们分析了一系列串联取代突变，涵盖了人TERT的这一区域的体外和体内功能。我们发现失活了端粒酶的生化和生物学功能的四个突变簇，被对酶活性影响很小或没有影响的突变隔开。我们还确定了一个区域，其中突变会产生催化活性但具有生物惰性的蛋白质。分离端粒酶（C-DAT）活性的C端区域似乎不参与核定位或蛋白质多聚化。相反，似乎在催化活性酶组装之后，C-DAT区域参与体内端粒合成的步骤。有趣的是，所有描述的区域都位于TERT的一部分中，该部分对于酵母中的细胞活力而言是可有可无的，这表明C末端在高等真核生物中的作用不同。

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