ATP-Dependent Chromatin Remodeling in Human Malignancy

人类恶性肿瘤中 ATP 依赖性染色质重塑

基本信息

  • 批准号:
    9900916
  • 负责人:
  • 金额:
    $ 21.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-07-10 至 2022-04-30
  • 项目状态:
    已结题

项目摘要

ABSTRACT Recent exome sequencing studies have found that over 20% of human cancers have deleterious mutations in the genes encoding the subunits of mSWI/SNF (BAF) complexes. A much larger number of tumors have amplifications or deletions of these genes. These complexes are polymorphic assemblies of 15 subunits encoded by 28 genes giving rise to remarkable combinatorial specificity. This biologic specificity is reflected in the highly selective pattern of oncogenic mutations in specific subunits in specific cancers. Cancer mutations generally have the characteristics of tumor suppressors and are generally heterozygous, implying that they play a genetically dominant role in suppressing tumor formation. Work in our lab and others has led to the conclusion that the ability of these complexes to oppose polycomb-mediated repression contributes to their roles in both development and oncogenesis. Hence, we will focus our work on the mechanisms underlying the opposition between BAF and polycomb and its therapeutic consequences. First we will use a novel, newly designed in vivo chromatin remodeling assay to fully characterize the nature of the opposition on a minute-by- minute basis. Secondly, we will define the energetic requirements for BAF-polycomb opposition and the essential role of ATP in regulating binding and release of PRC1 from BAF. Third, we will fully characterize the direct interaction between BAF and polycomb repressive complex 1 (PRC1) in terms of subunits and domains that are essential for this interaction. Fourth, we will explore the consequences of disruption of BAF-polycomb opposition for repair, recombination and transcription over the genome. Finally, we will define the therapeutic potential of a group of small molecule BAF inhibitors that we identified in earlier screens. At the conclusion of these studies we should have a mechanistic understanding of BAF-polycomb opposition and have explored at least two potential paths for the production of cancer-specific drugs.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Gerald R. Crabtree其他文献

Signaling through calcium, calcineurin, and NF-AT in lymphocyte activation and development.
在淋巴细胞激活和发育过程中通过钙、钙调神经磷酸酶和 NF-AT 发出信号。
lnterleukin-2-mediated elimination of the p27Kipl cyclin-dependent kinase inhibitor prevented by rapamycin
白细胞介素 2 介导的 p27Kipl 细胞周期蛋白依赖性激酶抑制剂的消除被雷帕霉素阻止
  • DOI:
    10.1038/372570a0
  • 发表时间:
    1994-12-08
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Jamison Nourse;Eduardo Firpo;W. Michael Flanagan;Steve Coats;Kornelia Polyak;Mong-Hong Lee;Joan Massague;Gerald R. Crabtree;James M. Roberts
  • 通讯作者:
    James M. Roberts
Signaling via GSK-3 is required during midline skeletogenesis
  • DOI:
    10.1016/j.ydbio.2006.04.337
  • 发表时间:
    2006-07-01
  • 期刊:
  • 影响因子:
  • 作者:
    Karen J. Liu;Joseph R. Arron;Kryn Stankunas;Gerald R. Crabtree
  • 通讯作者:
    Gerald R. Crabtree
Regulation of the regulators
监管者的监管
  • DOI:
    10.1038/35040690
  • 发表时间:
    2000-11-02
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Scott Stewart;Gerald R. Crabtree
  • 通讯作者:
    Gerald R. Crabtree
Regulation of the regulators
监管者的监管
  • DOI:
    10.1038/35040690
  • 发表时间:
    2000-11-02
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Scott Stewart;Gerald R. Crabtree
  • 通讯作者:
    Gerald R. Crabtree

Gerald R. Crabtree的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Gerald R. Crabtree', 18)}}的其他基金

HIJACKING CANCER DRIVERS TO ACTIVATE PROAPOPTOTIC GENES IN DLBCL
劫持癌症驱动者激活 DLBCL 中的促凋亡基因
  • 批准号:
    10564195
  • 财政年份:
    2022
  • 资助金额:
    $ 21.2万
  • 项目类别:
Small molecule regulation of endogenous transcription factors for circuit-specific neuromodulation
内源转录因子的小分子调节用于电路特异性神经调节
  • 批准号:
    10260250
  • 财政年份:
    2021
  • 资助金额:
    $ 21.2万
  • 项目类别:
ATP-Dependent Chromatin Remodeling in Human Malignancy
人类恶性肿瘤中 ATP 依赖性染色质重塑
  • 批准号:
    8371602
  • 财政年份:
    2012
  • 资助金额:
    $ 21.2万
  • 项目类别:
ATP-Dependent Chromatin Remodeling in Human Malignancy
人类恶性肿瘤中 ATP 依赖性染色质重塑
  • 批准号:
    9903224
  • 财政年份:
    2012
  • 资助金额:
    $ 21.2万
  • 项目类别:
ATP-Dependent Chromatin Remodeling in Human Malignancy
人类恶性肿瘤中 ATP 依赖性染色质重塑
  • 批准号:
    10586587
  • 财政年份:
    2012
  • 资助金额:
    $ 21.2万
  • 项目类别:
ATP-Dependent Chromatin Remodeling in Human Malignancy
人类恶性肿瘤中 ATP 依赖性染色质重塑
  • 批准号:
    9054819
  • 财政年份:
    2012
  • 资助金额:
    $ 21.2万
  • 项目类别:
ATP-Dependent Chromatin Remodeling in Human Malignancy
人类恶性肿瘤中 ATP 依赖性染色质重塑
  • 批准号:
    8508208
  • 财政年份:
    2012
  • 资助金额:
    $ 21.2万
  • 项目类别:
ATP-Dependent Chromatin Remodeling in Human Malignancy
人类恶性肿瘤中 ATP 依赖性染色质重塑
  • 批准号:
    8892817
  • 财政年份:
    2012
  • 资助金额:
    $ 21.2万
  • 项目类别:
Screen for Small Molecule Inhibitors of ATP Dependent Chromatin Remodeling
筛选 ATP 依赖性染色质重塑的小分子抑制剂
  • 批准号:
    8139341
  • 财政年份:
    2011
  • 资助金额:
    $ 21.2万
  • 项目类别:
Screen for Small Molecule Inhibitors of ATP Dependent Chromatin Remodeling
筛选 ATP 依赖性染色质重塑的小分子抑制剂
  • 批准号:
    8236903
  • 财政年份:
    2011
  • 资助金额:
    $ 21.2万
  • 项目类别:

相似海外基金

Discovery of nonnatural amino acids promoting alubmin binding
发现促进白蛋白结合的非天然氨基酸
  • 批准号:
    20K19926
  • 财政年份:
    2020
  • 资助金额:
    $ 21.2万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Engineering RNA-binding proteins with unnatural amino acids and expanded genetic codes
用非天然氨基酸和扩展遗传密码改造 RNA 结合蛋白
  • 批准号:
    511377-2017
  • 财政年份:
    2017
  • 资助金额:
    $ 21.2万
  • 项目类别:
    University Undergraduate Student Research Awards
Monitoring and Tuning a Gas-Binding Heme Protein with Unnatural Amino Acids
用非天然氨基酸监测和调节气体结合血红素蛋白
  • 批准号:
    9231766
  • 财政年份:
    2016
  • 资助金额:
    $ 21.2万
  • 项目类别:
Research Initiation Award: Toward Bionanoscience - Binding of Amino Acids with Graphene and N-doped Graphene
研究启动奖:迈向生物纳米科学——氨基酸与石墨烯和氮掺杂石墨烯的结合
  • 批准号:
    1601071
  • 财政年份:
    2016
  • 资助金额:
    $ 21.2万
  • 项目类别:
    Standard Grant
Unnatural Amino Acids of Tyrosine with Salicylic Acid into Cognate Peptide Binding Sequences to Observe Benefit in Cell-Permeability and Utility Towards Inhibitor Design
将酪氨酸的非天然氨基酸与水杨酸形成同源肽结合序列,以观察细胞渗透性和抑制剂设计实用性的益处
  • 批准号:
    443453-2013
  • 财政年份:
    2015
  • 资助金额:
    $ 21.2万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Unnatural Amino Acids of Tyrosine with Salicylic Acid into Cognate Peptide Binding Sequences to Observe Benefit in Cell-Permeability and Utility Towards Inhibitor Design
将酪氨酸的非天然氨基酸与水杨酸形成同源肽结合序列,以观察细胞渗透性和抑制剂设计实用性的益处
  • 批准号:
    443453-2013
  • 财政年份:
    2014
  • 资助金额:
    $ 21.2万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Unnatural Amino Acids of Tyrosine with Salicylic Acid into Cognate Peptide Binding Sequences to Observe Benefit in Cell-Permeability and Utility Towards Inhibitor Design
将酪氨酸的非天然氨基酸与水杨酸形成同源肽结合序列,以观察细胞渗透性和抑制剂设计实用性的益处
  • 批准号:
    443453-2013
  • 财政年份:
    2013
  • 资助金额:
    $ 21.2万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
IDENTIFICATION OF CONSERVED AMINO-ACIDS IN AN LPS BINDING CLEFT
LPS 结合裂缝中保守氨基酸的鉴定
  • 批准号:
    7164303
  • 财政年份:
    2005
  • 资助金额:
    $ 21.2万
  • 项目类别:
IDENTIFICATION OF CONSERVED AMINO-ACIDS IN AN LPS BINDING CLEFT
LPS 结合裂缝中保守氨基酸的鉴定
  • 批准号:
    6973859
  • 财政年份:
    2004
  • 资助金额:
    $ 21.2万
  • 项目类别:
IDENTIFICATION OF CONSERVED AMINO ACIDS IN AN LPS BINDING CLEFT
LPS 结合裂缝中保守氨基酸的鉴定
  • 批准号:
    6644340
  • 财政年份:
    2002
  • 资助金额:
    $ 21.2万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了