...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Sterile Alpha Motif Domain-Mediated Self-Association Plays an Essential Role in Modulating the Activity of the Drosophila ETS Family Transcriptional Repressor Yan
【24h】

Sterile Alpha Motif Domain-Mediated Self-Association Plays an Essential Role in Modulating the Activity of the Drosophila ETS Family Transcriptional Repressor Yan

机译：无菌Alpha母体域介导的自联想在调节果蝇ETS家族转录阻遏物的活性中起重要作用

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

摘要

The ETS family transcriptional repressor Yan is an important downstream target and effector of the receptor tyrosine kinase (RTK) signaling pathway in Drosophila melanogaster. Structural and biochemical studies have shown that the N-terminal sterile alpha motif (SAM) of Yan is able to self associate to form a helical polymeric structure in vitro, although the extent and functional significance of self-association of full-length Yan remain unclear. In this study, we demonstrated that full-length Yan self associates via its SAM domain to form higher-order complexes in living cells. Introduction of SAM domain missense mutations that restrict Yan to a monomeric state reduces Yan's transcriptional repression activity and impairs its function during embryonic and retinal development. Coexpression of combinations of SAM domain mutations that permit the formation of Yan dimers, but not higher-order oligomers, increases activity relative to that of monomeric Yan, but not to the level obtained with wild-type Yan. Mechanistically, self-association directly promotes transcriptional repression of target genes independent of its role in limiting mitogen-activated protein kinase (MAPK)-mediated phosphorylation and nuclear export of Yan. Thus, we propose that the formation of higher-order Yan oligomers contributes to proper repression of target gene expression and RTK signaling output in developing tissues.
机译：ETS家族的转录阻遏物Yan是果蝇果蝇中受体酪氨酸激酶（RTK）信号通路的重要下游靶标和效应子。结构和生化研究表明，Yan的N末端不育α基序（SAM）能够自我缔合形成体外螺旋聚合结构，尽管自我缔合的程度和功能意义全长严尚不清楚。在这项研究中，我们证明了全长的Yan通过其SAM结构域自缔合，从而在活细胞中形成更高阶的复合物。 SAM域错义突变的引入将Yan限制为单体状态，这会降低Yan的转录抑制活性，并削弱其在胚胎和视网膜发育过程中的功能。 SAM结构域突变组合的共表达允许形成Yan二聚体，但不能形成高阶寡聚物，相对于单体Yan，其活性增加，但未达到野生型Yan的水平。从机制上讲，自缔合直接促进靶基因的转录抑制，而独立于其在限制有丝分裂原激活的蛋白激酶（MAPK）介导的磷酸化和Yan核输出中的作用。因此，我们建议高阶Yan寡聚物的形成有助于在发展中的组织中适当抑制目标基因表达和RTK信号输出。

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