Transcriptional Activation of p62 by the master antioxidant NRF2 in EBV latency
EBV潜伏期主要抗氧化剂NRF2对p62的转录激活
基本信息
- 批准号:10726975
- 负责人:
- 金额:$ 8.24万
- 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:2023-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS related cancerAddressAgingAntioxidantsAutophagocytosisB-LymphocytesBiochemistry and Cellular BiologyBiomedical ResearchCancer BiologyCell Differentiation processCell LineCell SurvivalCell physiologyCessation of lifeClinicalDNA DamageDevelopmentDiseaseEBV-associated diseaseEpithelial CellsEpstein-Barr Virus InfectionsEpstein-Barr Virus latencyEpstein-Barr pathogenesisEquilibriumExperimental DesignsFlow CytometryGenetic TranscriptionGoalsHomeostasisHuman Herpesvirus 4I Kappa B-AlphaImageImmunityImmunologyInfection ControlInflammationLMP1Latent virus infection phaseLeftLymphoid CellLymphomaLyticMaintenanceMalignant NeoplasmsMediatingMitochondriaModelingMolecular and Cellular BiologyObesityOutcomeOxidation-ReductionOxidative StressParentsPathogenesisPathway interactionsPatientsPhosphorylationPhosphotransferasesProblem SolvingProcessProductionPropertyPublicationsPublishingQuantitative EvaluationsReactive Oxygen SpeciesRoleSeriesSignal TransductionStudentsTNFRSF5 geneTRAF6 geneTechniquesTestingTherapeuticThinkingTimeTrainingTranscription Factor AP-1Transcriptional ActivationViralViral PathogenesisVirusWritingbioimagingcell transformationdesignfascinateimprovedinterestneurotrophic factornovelnovel therapeutic interventionosteoclastogenesisp65parent projectpathogenresponsestudent trainingtranscription factortransforming virustumorigenesisvirus host interaction
项目摘要
Project Summary
EBV infection is associated with a panel of diseases and cancers, and serves as a fascinating paradigm for the
study of host-virus interactions. Oxidative stress is essential for virus-mediated oncogenesis, and for EBV
transformation of B cells. Reactive oxygen species (ROS) are independently induced by EBV-encoded products
LMP1, EBNA1/2, and EBERs in EBV latency. Our most recent publication shows for the first time that the master
antioxidant pathway Keap1-NRF2 is spontaneously activated in virus-transformed cells. With the support from the
parent R15, we have shown recently that LMP1 induces p62 expression via NFκB and AP1 axes. In this
supplementary project, we will test the hypothesis that EBV-produced ROS trigger the activation of the Keap1-
NRF2 pathway that represents an equally important mechanism for p62 induction in EBV latency. The objective
of this project is to address how the Keap1-NRF2 pathway is activated in EBV latency, and further define its role
in p62 (and other targets) transcriptional activation, with the long-term goal to identify novel factors that regulate
EBV-host interaction and may serve as potential context-specific targets for treating EBV-associated diseases and
malignancies. The proximate expected outcome of this project is the definition of novel roles of the Keap1-NRF2
antioxidant defense in EBV latent infection. This study is significant in that disclosing how EBV controls the balance
between oxidative stress and antioxidant defense will greatly improve our understanding of EBV latency and
pathogenesis. Long-term pursuits may develop strategies by targeting these processes and their interaction with
other cellular mechanisms for therapeutic applications.
项目摘要
EBV感染与一组疾病和癌症相关,并作为一个迷人的范例,
研究宿主与病毒的相互作用。氧化应激对于病毒介导的肿瘤发生和EBV
转化B细胞。活性氧(ROS)是由EBV编码的产物独立诱导的
EBV潜伏期中的LMP 1、EBNA 1/2和EBER。我们最近的出版物首次表明,
抗氧化途径Keap 1-NRF 2在病毒转化细胞中自发激活。的支持下
亲本R15,我们最近发现LMP 1通过NFκB和AP 1轴诱导p62表达。在这
作为补充项目,我们将测试EBV产生的ROS触发Keap 1激活的假设,
NRF 2通路代表EBV潜伏期中p62诱导的同等重要机制。客观
本项目的目的是解决Keap 1-NRF 2通路在EBV潜伏期中是如何激活的,并进一步确定其作用
在p62(和其他目标)转录激活,长期目标是确定新的因素,调节
EBV-宿主相互作用,并可作为治疗EBV相关疾病的潜在背景特异性靶点,
恶性肿瘤该项目的最接近的预期结果是定义Keap 1-NRF 2的新作用
EB病毒潜伏感染中的抗氧化防御。本研究对于揭示EBV如何控制这种平衡具有重要意义
氧化应激和抗氧化防御之间的联系将大大提高我们对EBV潜伏期的理解,
发病机制长期追求可以通过针对这些过程及其与
用于治疗应用的其他细胞机制。
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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{{ truncateString('Ling Wang', 18)}}的其他基金
The Ubiquitin Sensor p62 Is A Novel Component of EBV LMP1 Signalosome
泛素传感器 p62 是 EBV LMP1 信号体的新型成分
- 批准号:
10202127 - 财政年份:2021
- 资助金额:
$ 8.24万 - 项目类别:
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