Deciphering the phosphorylation pattern of RNA polymerase II for eukaryotic transcription

破译真核转录中 RNA 聚合酶 II 的磷酸化模式

基本信息

  • 批准号:
    10552217
  • 负责人:
  • 金额:
    $ 48.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-02-06 至 2028-01-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT The C-terminal domain (CTD) of the largest RNA polymerase II subunit is a unique CTD sequence (Y1S2P3T4S5P6S7) repeated many times and is mostly conserved in eukaryotes. This domain coordinates the recruitment of transcriptional factors to Pol II through its post-translational modifications, the loss of which cripples the highly efficient transcription process and causes the cell to die. The accurate phosphorylation state of different residues in the CTD heptad repeats by kinase and phosphatases is crucial to precisely recruiting proteins to mediate the transcription process. Our lab utilizes our extensive experience in protein chemistry to understand the precise pattern of phosphorylation during transcription by investigating the activity and specificity of these kinases and phosphatases. We seek to understand how the post-translational modifications of CTD are altered during biological events and how such changes are reflected in the outcome of transcription. We use multi-disciplinary methods including structural biology, biochemistry, mass spectrometry methodology, and global transcriptome analysis to investigate the molecular mechanism of how different modification states of RNA polymerase II coordinate the eukaryotic transcription. Equipped with extensive knowledge about the phosphatase function and activity, we further explore how the chemical inhibition of SCP1, a human phosphatase belonging to HAD superfamily, thwarts some of the growth glioblastoma cells. We utilized our experience in structural-based inhibitor design to identify covalent and non- covalent inhibitors targeting this unique phosphatase.
摘要

项目成果

期刊论文数量(0)
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Yan Jessie Zhang其他文献

RETRACTED ARTICLE: Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme
撤回文章:依赖α-酮戊二酸的单核非血红素铁酶形成内过氧化物
  • DOI:
    10.1038/nature15519
  • 发表时间:
    2015-11-02
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Wupeng Yan;Heng Song;Fuhang Song;Yisong Guo;Cheng-Hsuan Wu;Ampon Sae Her;Yi Pu;Shu Wang;Nathchar Naowarojna;Andrew Weitz;Michael P. Hendrich;Catherine E. Costello;Lixin Zhang;Pinghua Liu;Yan Jessie Zhang
  • 通讯作者:
    Yan Jessie Zhang

Yan Jessie Zhang的其他文献

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{{ truncateString('Yan Jessie Zhang', 18)}}的其他基金

Gene-specific transcriptional silencing directed by dephosphorylation of RNAP II
RNAP II 去磷酸化指导的基因特异性转录沉默
  • 批准号:
    9057573
  • 财政年份:
    2013
  • 资助金额:
    $ 48.92万
  • 项目类别:
Gene-specific transcriptional silencing by REST function
通过 REST 功能进行基因特异性转录沉默
  • 批准号:
    10237940
  • 财政年份:
    2013
  • 资助金额:
    $ 48.92万
  • 项目类别:
Gene-specific transcriptional silencing by REST function
通过 REST 功能进行基因特异性转录沉默
  • 批准号:
    10401469
  • 财政年份:
    2013
  • 资助金额:
    $ 48.92万
  • 项目类别:
Gene-specific transcriptional silencing directed by dephosphorylation of RNAP II
RNAP II 去磷酸化指导的基因特异性转录沉默
  • 批准号:
    8703729
  • 财政年份:
    2013
  • 资助金额:
    $ 48.92万
  • 项目类别:
Gene-specific transcriptional silencing by REST function
通过 REST 功能进行基因特异性转录沉默
  • 批准号:
    10386576
  • 财政年份:
    2013
  • 资助金额:
    $ 48.92万
  • 项目类别:
Gene-specific transcriptional silencing directed by dephosphorylation of RNAP II
RNAP II 去磷酸化指导的基因特异性转录沉默
  • 批准号:
    8578261
  • 财政年份:
    2013
  • 资助金额:
    $ 48.92万
  • 项目类别:
Discovery of Inhibitors for Small C-terminal Domain Phosphatases
小 C 端结构域磷酸酶抑制剂的发现
  • 批准号:
    8063541
  • 财政年份:
    2010
  • 资助金额:
    $ 48.92万
  • 项目类别:
Discovery of Inhibitors for Small C-terminal Domain Phosphatases
小 C 端结构域磷酸酶抑制剂的发现
  • 批准号:
    7926153
  • 财政年份:
    2010
  • 资助金额:
    $ 48.92万
  • 项目类别:

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