Role of RNA-Binding Proteins in BCR/ABL Leukemogenesis
RNA 结合蛋白在 BCR/ABL 白血病发生中的作用
基本信息
- 批准号:6792156
- 负责人:
- 金额:$ 24.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-08-15 至 2007-07-31
- 项目状态:已结题
- 来源:
- 关键词:RNA binding proteinSCID mouseSDS polyacrylamide gel electrophoresisactive sitesbiological signal transductioncarcinogenesischronic myelogenous leukemiaconfocal scanning microscopyflow cytometrygenetic translationgreen fluorescent proteinshematopoietic stem cellsheterogeneous nuclear ribonucleoproteinleukemiamass spectrometrymessenger RNAneoplasm /cancer geneticsphosphorylationpolymerase chain reactionprotein structure functionprotooncogenewestern blottings
项目摘要
DESCRIPTION (provided by applicant): Shuttling hnRNPs control the fate of eukaryotic mRNAs throughout their journey from the active site of transcription to that of translation; thus, gain or loss of their function in hematopoietic cells might result in altered hematopoiesis and/or emergence of leukemia. In BCR/ABL-expressing cells, there is a marked increase in the levels of different RNA binding proteins including FUS, hnRNP A1, hnRNP E2 and hnRNP K, four shuttling hnRNPs involved in the regulation of mRNA biogenesis, processing, nuclear export, and translation. Ectopic expression and/or inhibition of the activity of FUS, hnRNP A1 and hnRNP E2 affects the proliferation, survival, and differentiation of normal and BCR/ABL-expressing cells, suggesting that enhanced expression/activity of certain RNA-binding proteins plays an important but as yet unrecognized role in BCR/ABL leukemogenesis. Thus, the objective of this proposal is: 1) To investigate the mechanisms regulating hnRNP E2 and hnRNP A1 expression/function in BCR/ABL-expressing cells. 2) To identify hnRNP A1 and hnRNP E2-associated mRNAs encoding proteins differentially expressed in CML-blast crisis and CML-chronic phase cells. 3) To determine the BCR/ABL-dependent mechanisms regulating the expression/function of hnRNP K and determine whether hnRNP K function(s) is(are) required for BCR/ABL-induced leukemogenesis.
描述(由申请人提供):穿梭的hnRNPs控制着真核细胞mRNAs从转录活性部位到翻译活性部位的整个旅程;因此,它们在造血细胞中功能的获得或丧失可能导致造血改变和/或白血病的出现。在表达bcr/abl的细胞中,不同的RNA结合蛋白水平显著增加,包括FUS、hnRNP A1、hnRNP E2和hnRNP K,这四个穿梭的hnRNP参与调节mRNA的生物发生、加工、核输出和翻译。异位表达和/或抑制FUS、hnRNP A1和hnRNP E2的活性影响正常和bcr/abl表达细胞的增殖、存活和分化,提示某些RNA结合蛋白的表达/活性增强在bcr/abl白血病的发生中起着重要但尚未被认识的作用。因此,本建议的目的是:1)研究BCR/ABL表达细胞中hnRNP E2和hnRNP A1表达/功能的调控机制。2)鉴定在CML急变期和慢性期细胞中差异表达蛋白的hnRNP A1和hnRNP E2相关mRNAs。3)明确bcr/abl依赖的调节hnRNP K表达/功能的机制,并确定hnRNP K功能(S)是否参与bcr/abl诱导的白血病的发生。
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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Danilo Perrotti其他文献
Danilo Perrotti的其他文献
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{{ truncateString('Danilo Perrotti', 18)}}的其他基金
Role of SETBP1 in adult Ph+ acute lymphoblastic leukemia
SETBP1 在成人 Ph 急性淋巴细胞白血病中的作用
- 批准号:
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Role of microRNAs in the regulation of CML stem cell self renewal and survival
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Role of microRNAs in the regulation of CML stem cell self renewal and survival
microRNA在调节CML干细胞自我更新和存活中的作用
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Role of microRNAs in the regulation of CML stem cell self renewal and survival
microRNA在调节CML干细胞自我更新和存活中的作用
- 批准号:
9097613 - 财政年份:2014
- 资助金额:
$ 24.52万 - 项目类别:
Role of microRNAs in the regulation of CML stem cell self renewal and survival
microRNA在调节CML干细胞自我更新和存活中的作用
- 批准号:
9207740 - 财政年份:2014
- 资助金额:
$ 24.52万 - 项目类别:
Role of microRNAs in the regulation of CML stem cell survival and self renewal
microRNA在调节CML干细胞存活和自我更新中的作用
- 批准号:
8429383 - 财政年份:2012
- 资助金额:
$ 24.52万 - 项目类别:
Role of RNA-Binding Proteins in BCR/ABL Leukemogenesis
RNA 结合蛋白在 BCR/ABL 白血病发生中的作用
- 批准号:
6941638 - 财政年份:2003
- 资助金额:
$ 24.52万 - 项目类别:
Role of RNA-Binding Proteins in BCR/ABL Leukemogenesis
RNA 结合蛋白在 BCR/ABL 白血病发生中的作用
- 批准号:
7104977 - 财政年份:2003
- 资助金额:
$ 24.52万 - 项目类别:
Role of RNA-Binding Proteins in BCR/ABL Leukemogenesis
RNA 结合蛋白在 BCR/ABL 白血病发生中的作用
- 批准号:
6683061 - 财政年份:2003
- 资助金额:
$ 24.52万 - 项目类别:
Role of RNA Binding Proteins in BCR/ABL Leukemogenesis
RNA 结合蛋白在 BCR/ABL 白血病发生中的作用
- 批准号:
7763885 - 财政年份:2003
- 资助金额:
$ 24.52万 - 项目类别:
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