How HTLV-I Tax and HBZ control telomerase activity to induce adult T-cell leukemia
HTLV-I Tax 和 HBZ 如何控制端粒酶活性以诱导成人 T 细胞白血病
基本信息
- 批准号:9304181
- 负责人:
- 金额:$ 34.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:Adult Precursor T Lymphoblastic LeukemiaAdult T-Cell Leukemia/LymphomaAffectApoptoticBiologyBloodBreast FeedingCD4 Positive T LymphocytesCellsChildChronicDevelopmentDiseaseEtiologyEventFBXW7 geneFutureGenetic TranscriptionHela CellsHematological DiseaseHumanHuman ActivitiesHuman T-Cell Leukemia VirusesIn VitroIndividualInterferonsInterleukin-2JUN geneLaboratoriesLymphoblastic LeukemiaMaintenanceMalignant NeoplasmsMediatingMolecularMothersMutateMutationNF-kappa BOncogenicOncoproteinsPathway interactionsPatientsPost-Transcriptional RegulationProcessPublishingRegulationRegulatory PathwayRetroviridaeRoleSomatic CellSpinal Cord DiseasesT-Cell ProliferationT-Cell TransformationT-LymphocyteTP53 geneTaxesTelomeraseTelomere ShorteningTherapeuticTranscriptional ActivationViralVirusZidovudinebasec-myc Genescancer cellcarcinogenesiscell growthcell transformationdesignin vitro Assayin vivoleukemia/lymphomamutantneoplastic cellnext generation sequencingnoveloverexpressionpromoterreconstitutionsenescencetax Gene Productstherapeutic targettumorigenesisubiquitin ligase
项目摘要
PROJECT SUMMARY/ABSTRACT
The human T-cell leukemia virus type I (HTLV-I) is an onco-retrovirus that infects and transforms human CD4
T cells in vitro and in vivo. HTLV-I is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an
aggressive and invariably fatal hematological disease. The virus is transmitted through sexual contact,
contaminated blood and mother-to-child by breastfeeding, and is present in 20-30 million people worldwide.
HTLV-I-mediated T-cell transformation arises from a multi-step oncogenic process in which the virus induces
chronic T-cell proliferation, resulting in accumulation of genetic defects and deregulated cell growth. It is not yet
fully understood how HTLV-I engenders ATLL, but the virus blocks the apoptotic network and expends the
proliferative capacity of infected cells. HTLV-I infects and immortalizes primary human T cells in vitro and, after
several months, these cells acquire the ability to grow in the absence of interleukin-2, referred to as
transformation. We previously demonstrated that the viral oncogenic Tax can reactivate telomerase
expression, an event required for long-term proliferation of HTLV-I-transformed cells in vitro and in vivo. This
application will investigate the molecular events associated with deregulated telomerase activity and its role in
the HTLV-I transformation process. Since telomerase reactivation represents one of the central steps in human
carcinogenesis, results from this study will have broad application beyond viral oncogenesis.
项目摘要/摘要
人类T细胞白血病病毒I型(HTLV-I)是一种感染和转化人类CD4的肿瘤逆转录病毒
T细胞的体外和体内实验。HTLV-I是成人T细胞白血病/淋巴瘤(ATLL)的病原体。
侵袭性且总是致命的血液病。该病毒通过性接触传播,
通过母乳喂养污染了血液和母婴,全世界有2000-3000万人感染。
HTLV-I介导的T细胞转化源于病毒诱导的多步骤致癌过程
慢性T细胞增殖,导致遗传缺陷积聚和细胞生长失控。现在还不是
完全了解HTLV-I是如何产生ATL的,但该病毒阻断了细胞凋亡网络,并使
感染细胞的增殖能力。HTLV-I在体外感染并永生化原代人类T细胞,并在
几个月后,这些细胞在没有白细胞介素2的情况下获得生长的能力,称为
转型。我们先前证明了病毒致癌基因Tax可以重新激活端粒酶。
表达,这是HTLV-I转化细胞在体外和体内长期增殖所必需的事件。这
应用程序将研究与解除调节的端粒酶活性相关的分子事件及其在
HTLV-I转换过程。因为端粒酶重新激活是人类
致癌,这项研究的结果将在病毒致癌之外具有广泛的应用。
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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CHRISTOPHE P NICOT其他文献
CHRISTOPHE P NICOT的其他文献
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{{ truncateString('CHRISTOPHE P NICOT', 18)}}的其他基金
Role of Tax and HBZ in HTLV-1C replication in vivo
Tax 和 HBZ 在 HTLV-1C 体内复制中的作用
- 批准号:
10673788 - 财政年份:2022
- 资助金额:
$ 34.72万 - 项目类别:
Role of Tax and HBZ in HTLV-1C replication in vivo
Tax 和 HBZ 在 HTLV-1C 体内复制中的作用
- 批准号:
10526600 - 财政年份:2022
- 资助金额:
$ 34.72万 - 项目类别:
How HTLV-I Tax and HBZ control telomerase activity to induce adult T-cell leukemia
HTLV-I Tax 和 HBZ 如何控制端粒酶活性以诱导成人 T 细胞白血病
- 批准号:
9513500 - 财政年份:2016
- 资助金额:
$ 34.72万 - 项目类别:
Role of HTLV-I Tax-induced NF-kB in activation of ICN1 and immortalization of vir
HTLV-I Tax诱导的NF-kB在ICN1激活和vir永生化中的作用
- 批准号:
8435077 - 财政年份:2013
- 资助金额:
$ 34.72万 - 项目类别:
Role of HTLV-I Tax-induced NF-kB in activation of ICN1 and immortalization of vir
HTLV-I Tax诱导的NF-kB在ICN1激活和vir永生化中的作用
- 批准号:
8606171 - 财政年份:2013
- 资助金额:
$ 34.72万 - 项目类别:
Role of miR-124a in HTLV-I oncogenesis
miR-124a 在 HTLV-I 肿瘤发生中的作用
- 批准号:
8189473 - 财政年份:2011
- 资助金额:
$ 34.72万 - 项目类别:
Role of miR-124a in HTLV-I oncogenesis
miR-124a 在 HTLV-I 肿瘤发生中的作用
- 批准号:
8287054 - 财政年份:2011
- 资助金额:
$ 34.72万 - 项目类别:
Uncoupling of Jak/STAT in HTLV-1 associated leukemia
HTLV-1 相关白血病中 Jak/STAT 的解偶联
- 批准号:
7915825 - 财政年份:2009
- 资助金额:
$ 34.72万 - 项目类别:
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