Control of HIV-1 Transcription by CPSF6 and PP2A
CPSF6 和 PP2A 对 HIV-1 转录的控制
基本信息
- 批准号:10693519
- 负责人:
- 金额:$ 23.1万
- 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:2023-08-07 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:BiologyCDK9 Protein KinaseCellsCleavage And Polyadenylation Specificity FactorComplexDNA Polymerase IIEffectivenessFDA approvedGene ExpressionGenetic TranscriptionHIVHIV-1ImmuneIn VitroInfectionInvestigationMediatingMethodsMinorityMolecularOutputPersonsPhosphoric Monoester HydrolasesPhosphorylationProtein DephosphorylationProtein Phosphatase InhibitorProtein phosphataseProteinsProteolysisProteomicsProvirusesRNARegulationT-LymphocyteTestingTherapeutic AgentsTranscriptional RegulationViralVirus Latencycancer typedesignexperimental studyin vivoinnovationnovelnovel strategiesnovel therapeutic interventionnovel therapeuticspharmacologicpromoterreactivation from latencytoolubiquitin ligaseubiquitin-protein ligase
项目摘要
PROJECT SUMMARY
The major barrier toward the eradication of HIV-1 infection is the presence of a small reservoir of latently
infected cells that escape immune-mediated clearance. Due to the lack of transcriptional activity, latent
proviruses in vivo are not easily detectable and cannot be targeted by either natural immune mechanisms or
molecular therapies. Therefore, understanding how HIV-1 transcription is regulated will open doors to novel
therapeutic strategies targeting the latent reservoir.
Pharmacological approaches to reactivate the latent reservoir in vivo have been considered as potential
eradication therapies for more than a decade. However, the effectiveness of these approaches has been
disappointing as only a minority of latently infected cells appear to be responsive to latency-reversing agents. A
deeper understanding of the transcriptional regulation of the HIV-1 promoter is necessary before we can design
novel and effective LRAs. Cleavage and polyadenylation specificity factor 6 (CPSF6) is a cellular protein with
multiple functions both in cellular and viral biology. Our recent finding that CPSF6 controls the stability and activity
of PP2A, a phosphatase directly implicated in the de-phosphorylation and inactivation of CDK9 and RNA Pol II,
reveals an exciting new line of investigation into potential cure strategies. This proposal will focus on the following
innovative directions: (a) to further understand the factors regulating HIV-1 transcription, with a focus on CPSF6
and PP2A; (b) to explore the possibility of using PP2A inhibition as a method to reactivate latent viruses; and (3)
to further explore the unknown functions of CPSF6 based on a recent proteomics experiment from our group
yielding several exciting hits.
项目总结
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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VICENTE PLANELLES的其他文献
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9203550 - 财政年份:2016
- 资助金额:
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8326800 - 财政年份:2011
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An Ex Vivo Model of HIV-1 Latency and Reactivation using Primary Memory Cells
使用原代记忆细胞的 HIV-1 潜伏期和再激活的离体模型
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8212276 - 财政年份:2010
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An Ex Vivo Model of HIV-1 Latency and Reactivation using Primary Memory Cells
使用原代记忆细胞的 HIV-1 潜伏期和再激活的离体模型
- 批准号:
8613428 - 财政年份:2010
- 资助金额:
$ 23.1万 - 项目类别:
An Ex Vivo Model of HIV-1 Latency and Reactivation using Primary Memory Cells
使用原代记忆细胞的 HIV-1 潜伏期和再激活的离体模型
- 批准号:
8418764 - 财政年份:2010
- 资助金额:
$ 23.1万 - 项目类别:
An Ex Vivo Model of HIV-1 Latency and Reactivation using Primary Memory Cells
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8019124 - 财政年份:2010
- 资助金额:
$ 23.1万 - 项目类别: