• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>other >Hepatoma Derived Growth Factor represses SET and MYND domain containing 1 gene expression through interaction with C-terminal binding protein
【2h】

Hepatoma Derived Growth Factor represses SET and MYND domain containing 1 gene expression through interaction with C-terminal binding protein

机译：肝癌衍生生长因子通过与C末端结合蛋白相互作用来抑制含有1个基因表达的SET和MYND结构域

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Hepatoma Derived Growth Factor (HDGF) is a nuclear protein with both mitogenic and angiogenic activity, it is highly expressed in the developing heart and vasculature. To date the mechanisms of HDGF’s function are unknown. Oligonucleotide microarray analysis was used to gain insights into HDGF function. Adenoviral expression of HDGF significantly (≥ 2 fold) downregulated a large group (66) of genes, and increased expression of a relatively small number of genes (9). Two groups of target genes which are involved in cardiovascular development and transcriptional regulation were validated by real time PCR, including the skeletal/cardiac muscle specific SET and MYND domain containing 1 (SMYD1) gene. This suggested that HDGF could function as a transcriptional repressor. In a one-hybrid system, GBD-HDGF significantly repressed reporter gene activity in a dose dependent manner. This demonstrated that HDGF has transcriptional repressive activity. Moreover, in G-7 myoblast cells, overexpression of a GFP-HDGF fusion specifically downregulated SMYD1 mRNA expression and the activity of the human SMYD1 promoter. HDGF repressed SMYD1 gene transcription through interaction with a transcriptional corepressor C-terminal binding protein (CtBP). Overexpressing of CtBP potentiated the trans-repressive activity of HDGF; on the other hand, knocking down CtBP attenuated the trans-repressive effect of HDGF. HDGF binds CtBP through a non-canonical binding motif (PKDLF) within the PWWP domain, as substitutional mutation of DL to AS abolished HDGF and CtBP interaction and diminished the trans-repressive effect of HDGF without affecting DNA binding. Finally, fluorescent microscopy studies showed that HDGF induced the nuclear accumulation of CtBP suggesting that HDGF forms a transcriptional complex with CtBP. Taken together, our data demonstrate that HDGF functions as a transcriptional repressor of the SMYD1 gene, through interaction with the transcriptional corepressor CtBP. Because of moderate conservation of the CtBP binding motif in HDGF family members, trans-repressive activity mediated by CtBP may be a common function among HDGF proteins.
机译：肝癌衍生生长因子（HDGF）是一种核蛋白，具有促有丝分裂和血管生成活性，在发育中的心脏和脉管系统中高度表达。迄今为止，HDGF功能的机制尚不清楚。寡核苷酸微阵列分析用于深入了解HDGF功能。 HDGF的腺病毒表达显着（≥2倍）下调了一大批基因（66个），并增加了相对少数基因的表达（9个）。通过实时PCR验证了涉及心血管发育和转录调控的两组靶基因，包括骨骼肌/心肌特异性SET和含有1个SMYD1基因的MYND结构域。这表明HDGF可以充当转录阻遏物。在单杂交系统中，GBD-HDGF以剂量依赖性方式显着抑制报告基因的活性。这证明HDGF具有转录抑制活性。此外，在G-7成肌细胞中，GFP-HDGF融合蛋白的过表达特异性下调了SMYD1 mRNA的表达和人类SMYD1启动子的活性。 HDGF通过与转录共抑制因子C末端结合蛋白（CtBP）相互作用来抑制SMYD1基因转录。 CtBP的过表达增强了HDGF的反式表达活性。另一方面，降低CtBP减弱了HDGF的反式抑制作用。 HDGF通过PWWP域内的非经典结合基序（PKDLF）与CtBP结合，因为DL对AS的取代突变消除了HDGF和CtBP的相互作用，并降低了HDGF的反式抑制作用，而不会影响DNA结合。最后，荧光显微镜研究表明HDGF诱导了CtBP的核积累，表明HDGF与CtBP形成了转录复合体。两者合计，我们的数据表明，HDGF通过与转录共抑制因子CtBP相互作用而充当SMYD1基因的转录抑制因子。由于在HDGF家族成员中CtBP结合基序的中等保守性，由CtBP介导的反式抑制活性可能是HDGF蛋白之间的共同功能。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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