SV40 Large T and Rb Effects on E2F Dependent Genes
SV40 大 T 和 Rb 对 E2F 依赖性基因的影响
基本信息
- 批准号:8233034
- 负责人:
- 金额:$ 25.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-04-01 至 2014-03-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAdenovirusesAffectAntigensBindingBiological AssayCell CycleCellsChromatinComplexDataDrosophila snf proteinE2F transcription factorsE2F1 geneEP300 geneElementsEmbryoEnzymesEventFamilyFibroblastsGene ExpressionGene TargetingGenesGenetic TranscriptionGenomicsHPV E7Histone AcetylationHistonesImmunoprecipitationInfectionKnock-outKnockout MiceLaboratoriesLarge T AntigenModelingOncogene ProteinsOncogenic VirusesPapovaviridaePlayPrincipal InvestigatorProteinsProteomicsRB1 geneRBL2 geneRecruitment ActivityReportingRepressionRoleSMARCA2 geneSMARCA4 geneSimian virus 40TimeTransactivationViralViral OncogeneVirusWorkantigen bindingbasechromatin immunoprecipitationgenome-wideinsightpreferenceprogramspromotertransforming virus
项目摘要
Recent observations have suggested that the viral oncoproteins SV40 Large T antigen (SV40LT) and
Adenovirus E1A play a direct role in transactivation of E2F-dependent genes to promote cell cycle entry. We
propose that SV40LT transformation is dependent on its ability to directly transactivate E2F-dependent
promoters by binding to chromatin-bound Rb, p107 and p130, thereby recruiting CBP and p300 to activate
E2F transcription. In addition, our understanding of how the Rb family controls E2F-dependent gene
expression has continued to evolve. Using a sensitive proteomic approach, we confirmed that Rb binds to
the BRG1 and BRM family of SWI/SNF proteins. However, it is not known if Rb recruits the BRG1/BRM
complex to E2F promoters and if they serve to activate E2F dependent gene expression. To address these
questions, we propose the following specific aims.
Specific Aim 1. Determine if SV40LT can directly transactivate E2F promoters. We will perform
Chromatin immunoprecipitation (ChIP) for SV40LT antigen on selected E2F dependent promoters. We will
identify the host cell factors required for SV40LT binding to E2F-dependent promoters using knockout MEFs
and determine if the known transforming domains of SV40LT contribute to E2F transactivation.
Specific Aim 2. Determine if Rb recruits the BRG1/BRM complex to affect E2F activity during
quiescence and proliferation. We will determine the ability of the Rb-BRG1/BRM complex to bind specifically
to E2F promoters and whether the complex contributes to activation or repression of E2F transcription.
Specific Aim 3. Determine if SV40LT selectively activates E2F promoters to promote entry into the cell
cycle. We will perform ChIP using genomic tiling arrays (ChlP-chip) for SV40LT to identify promoter
elements that SV40LT selectively binds. These results will be compared with ChlP-chip for Rb, p130, p107,
E2F1, E2F2, E2F3 and E2F4. This approach will be used to determine if SV40LT activates all or a subset of
E2F promoters to promote cell cycle entry and transformation.
最近的观察表明,病毒癌蛋白SV 40大T抗原(SV 40 LT)和
腺病毒E1 A在E2 F依赖基因的反式激活中发挥直接作用,以促进细胞进入周期。我们
我提出SV 40 LT转化依赖于其直接反式激活E2 F依赖性的能力,
通过结合染色质结合的Rb,p107和p130,从而募集CBP和p300激活启动子,
E2 F转录。此外,我们对Rb家族如何控制E2 F依赖基因的理解,
表达方式不断演变。使用敏感的蛋白质组学方法,我们证实Rb与
SWI/SNF蛋白的BRG 1和BRM家族。然而,不知道Rb是否募集BRG 1/BRM
复合物的E2 F启动子,如果它们用于激活E2 F依赖性基因表达。解决这些
针对这些问题,我们提出以下具体目标。
具体目标1.确定SV 40 LT是否可以直接反式激活E2 F启动子。我们将执行
在选定的E2 F依赖性启动子上进行SV 40 LT抗原的染色质免疫沉淀(ChIP)。我们将
使用敲除MEF鉴定SV 40 LT与E2 F依赖性启动子结合所需的宿主细胞因子
并确定SV 40 LT的已知转化结构域是否有助于E2 F反式激活。
具体目标2。确定Rb是否募集BRG 1/BRM复合物以影响E2 F活性,
静止和增殖。我们将确定Rb-BRG 1/BRM复合物特异性结合
E2 F启动子以及复合物是否有助于激活或抑制E2 F转录。
具体目标3。确定SV 40 LT是否选择性激活E2 F启动子以促进进入细胞
周期我们将使用SV 40 LT的基因组平铺阵列(ChIP-芯片)进行ChIP以鉴定启动子
SV 40 LT选择性结合的元件。将这些结果与Rb、p130、p107、
E2 F1、E2 F2、E2 F3和E2 F4。该方法将用于确定SV 40 LT是否激活所有或部分
E2 F启动子促进细胞周期进入和转化。
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)
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James A. DeCaprio其他文献
The DREAM complex: master coordinator of cell cycle-dependent gene expression
DREAM 复合物:细胞周期依赖性基因表达的主要协调者
- DOI:
10.1038/nrc3556 - 发表时间:
2013-07-11 - 期刊:
- 影响因子:66.800
- 作者:
Subhashini Sadasivam;James A. DeCaprio - 通讯作者:
James A. DeCaprio
IMPDH inhibition induces DNA replication stress and ATR sensitivity in Merkel cell carcinoma
IMPDH抑制在默克尔细胞癌中诱导DNA复制应激和ATR敏感性
- DOI:
10.1016/j.isci.2025.112567 - 发表时间:
2025-06-20 - 期刊:
- 影响因子:4.100
- 作者:
Julia L. Schnabel;Thomas C. Frost;Adam C. Wang;Varsha Ananthapadmanabhan;Satvik Gurram;Kara M. Soroko;Prafulla C. Gokhale;James A. DeCaprio - 通讯作者:
James A. DeCaprio
Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC
- DOI:
10.1007/s00262-017-2099-3 - 发表时间:
2017-11-30 - 期刊:
- 影响因子:5.100
- 作者:
Jürgen C. Becker;Andreas Stang;Axel zur Hausen;Nicole Fischer;James A. DeCaprio;Richard W. Tothill;Rikke Lyngaa;Ulla Kring Hansen;Cathrin Ritter;Paul Nghiem;Christopher K. Bichakjian;Selma Ugurel;David Schrama - 通讯作者:
David Schrama
Milademetan is a highly potent MDM2 inhibitor in TP53 wild-type (p53 WT) models of Merkel cell carcinoma (MCC)
- DOI:
10.1016/j.jid.2022.08.004 - 发表时间:
2022-10-01 - 期刊:
- 影响因子:
- 作者:
Varsha Ananthapadmanabhan;Thomas C. Frost;Kara M. Soroko;Aine Knott;Brianna Magliozzi;Prafulla C. Gokhale;Vijaya Tirunagaru;Robert C. Doebele;James A. DeCaprio - 通讯作者:
James A. DeCaprio
Association between treatment center experience and survival after diagnosis of stage I to III Merkel cell carcinoma treated with surgery with or without postoperative radiation therapy
- DOI:
10.1016/j.jaad.2020.10.089 - 发表时间:
2021-03-01 - 期刊:
- 影响因子:
- 作者:
Fallon E. Chipidza;Manisha Thakuria;Jonathan D. Schoenfeld;Ann W. Silk;Paul J. Catalano;Charles H. Yoon;Glenn J. Hanna;James A. DeCaprio;Roy B. Tishler;Danielle N. Margalit - 通讯作者:
Danielle N. Margalit
James A. DeCaprio的其他文献
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{{ truncateString('James A. DeCaprio', 18)}}的其他基金
Identification of Novel Oncogenic Signaling Pathways using Viral Perturbations
利用病毒扰动鉴定新型致癌信号通路
- 批准号:
10460971 - 财政年份:2019
- 资助金额:
$ 25.47万 - 项目类别:
Identification of Novel Oncogenic Signaling Pathways using Viral Perturbations
利用病毒扰动鉴定新型致癌信号通路
- 批准号:
10411425 - 财政年份:2019
- 资助金额:
$ 25.47万 - 项目类别:
Identification of Novel Oncogenic Signaling Pathways using Viral Perturbations
利用病毒扰动鉴定新型致癌信号通路
- 批准号:
10664906 - 财政年份:2019
- 资助金额:
$ 25.47万 - 项目类别:
Identification of Novel Oncogenic Signaling Pathways using Viral Perturbations
利用病毒扰动鉴定新型致癌信号通路
- 批准号:
9816351 - 财政年份:2019
- 资助金额:
$ 25.47万 - 项目类别:
Identification of Novel Oncogenic Signaling Pathways using Viral Perturbations
利用病毒扰动鉴定新型致癌信号通路
- 批准号:
10222618 - 财政年份:2019
- 资助金额:
$ 25.47万 - 项目类别:
Young Empowered Scientists for ContinUed Research Engagement (YES for CURE)
赋权年轻科学家继续参与研究(CURE 是)
- 批准号:
9416355 - 财政年份:2017
- 资助金额:
$ 25.47万 - 项目类别:
PROJECT 1: Merkel Cell Carcinoma, Merkel Cell Polyomavirus and PP2A (James A. DeCaprio)
项目 1:默克尔细胞癌、默克尔细胞多瘤病毒和 PP2A (James A. DeCaprio)
- 批准号:
9981670 - 财政年份:2017
- 资助金额:
$ 25.47万 - 项目类别:
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