课题基金 / 基金详情

项目摘要

项目成果

Maha Abdellatif的其他基金

相似基金

相关文献

中文摘要
翻译
描述(申请人提供):在这项提案中,我们将确定Ras GTP酶激活蛋白(RasGAP)在心肌肥厚过程中调节microRNA-1(miR-1)的作用。MIR-1是一种转录后基因表达调节因子,在工作超负荷、生长因子或RasGAP诱导肥大时急剧下调,这是心肌细胞生长所必需的结果。我们的初步数据表明,RasGAP SH3结合蛋白(G3BP)以RasGAP和Akt依赖的方式与miR-1结合。我们假设,肥大刺激诱导Akt介导的G3BP磷酸化,并随后被RasGAP-丝氨酸复合体募集。这使得它非常接近miR-1,在那里它结合并水解早熟的miR-1。随后,miR-1的下调导致其靶标上调,其中包括:RasGAP、CDK9、纤维连接蛋白、内皮素和胰岛素样生长因子等。这些基因在心肌肥厚的发生发展中起着关键作用。因此,我们的目标是:1)研究RasGAP介导的miR-1在心肌细胞肥大过程中下调的机制。为此,我们将利用培养的心肌细胞与重组cDNA、腺病毒和启动子构建物结合,使用STRAND作为肥大刺激:A.检测G3BP在miR-1转录后调控中的作用,B.检测Akt在RasGAP-G3BP调控的miR-1稳定性中的作用,C.研究细丝-C在RasGAP-G3BP招募中的作用,D.研究肥大和RasGAP激活的途径对miR-1转录和转录后调控的影响。目的2)研究RasGAP和miR-1在小鼠心肌肥厚中的作用。
英文摘要
DESCRIPTION (provided by applicant): In this proposal we will determine the role of Ras GTPase-activating protein (RasGAP) in regulating microRNA-1 (miR-1) during cardiac hypertrophy. MiR-1 is a post- transcriptional regulator of gene expression that is acutely down-regulated upon induction of hypertrophy by work overload, growth factors, or RasGAP, an outcome that is necessary for myocyte growth. Our preliminary data show that RasGAP SH3-binding protein (G3BP) binds miR-1 in a RasGAP- and Akt-dependent manner. We hypothesize that hypertrophic stimuli induce Akt-mediated G3BP phosphorylation and its subsequent recruitment by RasGAP-filamin complex. This brings it into close proximity to miR-1, where it binds and hydrolyzes premature miR-1. Subsequently, down-regulation of miR- 1 results in upregulation of its targets that include: RasGAP, Cdk9, fibronectin, endothelin, and insulin-like growth factor, among others. These genes play a critical role in the development of cardiac hypertrophy. Thus, our Aims are: 1) to study the mechanism of RasGAP-mediated down-regulation of miR-1 during myocyte hypertrophy. For this aim we will utilize cultured myocytes in conjunction with recombinant cDNA, adenoviruses, and promoter constructs, using stretch as a hypertrophic stimulus to: a. examine the role of G3BP in post-transcriptional regulation of miR-1, b. examine the role of Akt in RasGAP-G3BP-regulated miR-1 stability, c. examine the role of filamin-C in recruitment of RasGAP-G3BP, d. examine the effect of hypertrophy and the RasGAP- activated pathway on transcriptional vs. post-transcriptional regulation of miR-1. Aim 2) to study the role of RasGAP and miR-1 during cardiac hypertrophy in a mouse model.
期刊论文(9)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1161/circresaha.111.247437
发表时间: 2012-02-17
期刊: Circulation research
影响因子: 20.1
作者: [Abdellatif M]
通讯作者: Abdellatif M
DOI: 10.1016/j.cellsig.2010.02.008
发表时间: 2010-07
期刊: Cellular signalling
影响因子: 4.8
作者: [Rane S, He M, Sayed D, Yan L, Vatner D, Abdellatif M]
通讯作者: Abdellatif M
The regulation of the histone code during cardiac hypertrophy
  • 批准号:
    10373727
  • 项目类别:
  • 资助金额:
    $66.54万
  • 财政年份:
    2021
  • 负责人:
    Maha Abdellatif
  • 依托单位:
The regulation of the histone code during cardiac hypertrophy
Transcriptional mechanisms in cardiac hypertrophy
  • 批准号:
    10335218
  • 项目类别:
  • 资助金额:
    $63.77万
  • 财政年份:
    2020
  • 负责人:
    Maha Abdellatif
  • 依托单位:
Transcriptional mechanisms in cardiac hypertrophy
  • 批准号:
    9893424
  • 项目类别:
  • 资助金额:
    $63.36万
  • 财政年份:
    2020
  • 负责人:
    Maha Abdellatif
  • 依托单位:
海外基金