Regulation and function of the YAP transcription co-activator oncoprotein

YAP转录辅激活癌蛋白的调控和功能

基本信息

  • 批准号:
    8627562
  • 负责人:
  • 金额:
    $ 30.26万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-04-08 至 2018-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The Hippo tumor suppressor pathway functions to limit tissue growth and organ size by inhibiting proliferation and inducing apoptosis. Dysregulation of the Hippo pathway contributes to tumorigenesis. The key downstream effectors of the Hippo pathway are the transcription co-activator YAP, which is phosphorylated and inhibited by the Hippo pathway kinase Lats. YAP overexpression and hyperactivation are found in human cancers. Extensive studies have identified many intracellular proteins that modulate the Hippo pathway. However, key questions regarding the extracellular signals and cell surface receptors for the Hippo pathway have not been addressed. We recently discovered that G-protein coupled receptors (GPCR) and their cognate ligands regulate the Hippo pathway. GPCR modulates many intracellular signaling molecules including protein kinase A (PKA) and protein kinase C (PKC). PKA is activated by cAMP, a second messenger that is elevated by stimulation of Gs-coupled receptor. PKC is activated by diacylglycerol that is also a second messenger elevated by Gq/11- coupled receptors. Both PKA and PKC are involved in a wide range of cellular regulation, including gene expression and cell growth. Our preliminary studies reveal that PKA and PKC potently modulate YAP. PKA inhibits YAP by increasing phosphorylation while PKC activates YAP by inducing dephosphorylation. The long- term goal of this project is to elucidate the mechanism of YAP regulation by PKA and PKC, to understand the regulation and function of the Hippo-YAP pathway in cell growth, organ size, tumorigenesis and cancer metastasis, and to provide potential therapeutic targets for cancer treatment.
描述(由申请人提供):Hippo肿瘤抑制途径通过抑制增殖和诱导凋亡来限制组织生长和器官大小。Hippo通路的失调有助于肿瘤发生。Hippo途径的关键下游效应物是转录共激活因子雅普,其被磷酸化并被Hippo途径激酶Lats抑制。在人类癌症中发现雅普过表达和过度活化。广泛的研究已经确定了许多调节Hippo通路的细胞内蛋白。然而,关于Hippo通路的细胞外信号和细胞表面受体的关键问题尚未得到解决。我们最近发现,G蛋白偶联受体(GPCR)及其同源配体调节Hippo通路。GPCR调节许多细胞内信号分子,包括蛋白激酶A(PKA)和蛋白激酶C(PKC)。PKA被cAMP激活,cAMP是一种第二信使,通过刺激GS偶联受体而升高。PKC被甘油二酯激活,甘油二酯也是Gq/11偶联受体升高的第二信使。PKA和PKC都参与广泛的细胞调节,包括基因表达和细胞生长。我们的初步研究表明PKA和PKC对雅普有很强的调节作用。PKA通过增加磷酸化抑制雅普,而PKC通过诱导去磷酸化激活雅普。本项目的长期目标是阐明PKA和PKC对雅普的调控机制,了解Hippo-雅普通路在细胞生长、器官大小、肿瘤发生和肿瘤转移中的调控和功能,为肿瘤治疗提供潜在的治疗靶点。

项目成果

期刊论文数量(0)
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Kun-Liang Guan其他文献

Kun-Liang Guan的其他文献

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{{ truncateString('Kun-Liang Guan', 18)}}的其他基金

Functional interplay between Hippo and estrogen receptor ESR1
Hippo 和雌激素受体 ESR1 之间的功能相互作用
  • 批准号:
    10339901
  • 财政年份:
    2022
  • 资助金额:
    $ 30.26万
  • 项目类别:
Molecular Mechanism and Therapy for Ocular Melanoma
眼部黑色素瘤的分子机制及治疗
  • 批准号:
    9453662
  • 财政年份:
    2017
  • 资助金额:
    $ 30.26万
  • 项目类别:
Molecular Mechanism and Therapy for Ocular Melanoma
眼部黑色素瘤的分子机制及治疗
  • 批准号:
    9328539
  • 财政年份:
    2017
  • 资助金额:
    $ 30.26万
  • 项目类别:
The mTOR and Hippo pathway in cell growth and cancer
mTOR 和 Hippo 通路在细胞生长和癌症中的作用
  • 批准号:
    9752481
  • 财政年份:
    2015
  • 资助金额:
    $ 30.26万
  • 项目类别:
The mTOR and Hippo pathway in cell growth and cancer
mTOR 和 Hippo 通路在细胞生长和癌症中的作用
  • 批准号:
    9120339
  • 财政年份:
    2015
  • 资助金额:
    $ 30.26万
  • 项目类别:
Regulation of the Hippo pathway and its role in uveal melanoma
Hippo通路的调节及其在葡萄膜黑色素瘤中的作用
  • 批准号:
    8722567
  • 财政年份:
    2012
  • 资助金额:
    $ 30.26万
  • 项目类别:
Regulation of the Hippo pathway and its role in uveal melanoma
Hippo通路的调节及其在葡萄膜黑色素瘤中的作用
  • 批准号:
    8529541
  • 财政年份:
    2012
  • 资助金额:
    $ 30.26万
  • 项目类别:
Regulation of the Hippo pathway and its role in uveal melanoma
Hippo通路的调节及其在葡萄膜黑色素瘤中的作用
  • 批准号:
    8340411
  • 财政年份:
    2012
  • 资助金额:
    $ 30.26万
  • 项目类别:
Protein phosphorylation and growth factor function
蛋白质磷酸化和生长因子功能
  • 批准号:
    7892688
  • 财政年份:
    2009
  • 资助金额:
    $ 30.26万
  • 项目类别:
Regulation and function of the YAP transcription co-activator oncoprotein
YAP转录辅激活癌蛋白的调控和功能
  • 批准号:
    8022881
  • 财政年份:
    2008
  • 资助金额:
    $ 30.26万
  • 项目类别:

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