CONTROL OF C MYC TRANSCRIPTION IN HIGH GRADE LYMPHOMAS
CONTROL OF C MYC TRANSCRIPTION IN HIGH GRADE LYMPHOMAS
批准号:
2871876
负责人:
LINDA M BOXER
金额:
$18.9万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-04-15 至 2001-01-31
关键词:
B lymphocyte Burkitt's lymphoma DNA binding protein DNA footprinting DNA methylation chemical binding chromosome translocation crosslink gene expression genetic models genetic transcription human tissue immunoglobulin genes immunoprecipitation lymphoma neoplasm /cancer genetics neoplastic transformation nucleic acid hybridization oncogenes protooncogene tissue /cell culture transcription factor transfection
中文摘要
描述:(改编自调查人员摘要)申请人
建议从分子水平研究c-myc的激活机制。
Burkitt淋巴瘤和转化性淋巴瘤中
T(8;14)易位。我们的目标是更好地理解
B细胞恶变的机制。
A.转录调控分子机制的鉴定
C-myc基因在B细胞中的表达。体内足迹和体外足迹
蛋白质-DNA结合研究将用于定位调控区域
C-myc在正常B细胞和B细胞系中的重要表达
不含t(8;14)易位的基因。这些人的身份
体内结合的蛋白质将通过紫外光技术确定
交联法和免疫沉淀法,然后杂交分析。
将对现场进行功能评估,包括临时
在B细胞系中进行了基因转导实验。
B.转录调控分子机制的鉴定
伯基特淋巴瘤的c-myc基因。条件一直是
优化了易位与正常c-myc的分离
伯基特的几个细胞系中的基因。在约束方面的差异
已经发现了两个等位基因之间的转录因子,这些
我们会继续进行研究。金黄色葡萄球菌的鉴定与表征
体内结合的蛋白质将按照A.
将比较每个等位基因的甲基化状态。
C.转录调控分子机制的鉴定
C-myc和bcl2基因在转化性淋巴瘤及其低表达中的表达
级别对应。C-myc和bc1-2的解除调控
免疫球蛋白基因座的研究将如B。
D.调控基因中发现的突变对c-myc表达的影响
地区。任何突变对调节性蛋白结合的影响
蛋白质将通过体内和体外研究进行研究。
E.免疫球蛋白基因座在c-myc激活中的作用
表情。复制c-myc易位的模型构建
将被构造并用于定义
免疫球蛋白基因座。
这项提案的成功完成将是第一个
例如,参与转录的分子机制
通过易位激活癌基因是已知的。抄写
将确定激活c-myc所需的因子。
以及免疫球蛋白基因座上负责
这将被定义。
英文摘要
DESCRIPTION: (adapted from the investigator's abstract) The applicant
proposes to study the mechanism of activation of c-myc at a molecular
level in both Burkitt's lymphoma and transformed lymphomas with the
t(8;14) translocation. The goal is to reach a better understanding of
the mechanisms of malignant transformation of B cells.
A. Identification of the molecular mechanisms of transcriptional control
of the c-myc gene in B cells. In vivo footprinting and in vitro
protein-DNA binding studies will be used to locate regulatory regions
important for c-myc expression in normal B cells and in B cell lines
that do not contain the t(8;14) translocation. The identity of the
proteins that bind in vivo will be determined by a technique of UV
crosslinking and immunoprecipitation followed by hybridization analysis.
Functional assessment of the sites will be performed with transient
transfection experiments in B cell lines.
B. Identification of the molecular mechanisms of transcriptional control
of the c-myc gene in Burkitt's lymphomas. Conditions have been
optimized for the separation of the translocation from the normal c-myc
gene in several Burkitt's cell lines. Differences in the binding of
transcription factors between the two alleles have been found and these
studies will be continued. The identification and characterization of
the proteins that bind in vivo will be determined as described in A.
The methylation status of each allele will be compared.
C. Identification of the molecular mechanisms of transcriptional control
of the c-myc and bcl-2 genes in transformed lymphomas and their low
grade counterparts. The deregulation of both c-myc and bcl-2 by the
immunoglobulin locus will be studied as outlined in B.
D. Effect on c-myc expression of mutations identified in the regulatory
regions. The effects of any mutations on the binding of regulatory
proteins will be investigated by in vivo and in vitro studies.
E. Role of the immunoglobulin locus in the activation of c-myc
expression. Model constructs which reproduce the c-myc translocations
will be constructed and used to define the important regions of the
immunoglobulin locus.
The successful completion of this proposal will represent the first
instance where the molecular mechanisms involved in the transcriptional
activation of an oncogene by translocation are known. The transcription
factors that are required for the activation of c-myc will be identified
and the regions of the immunoglobulin locus which are responsible for
this will be defined.
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会议论文
Activation of BCL-2 in Hematologic Malgnancies
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批准号:7483462
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项目类别:
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资助金额:$29.49万
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财政年份:2007
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负责人:LINDA M BOXER
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依托单位:
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批准号:7902054
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资助金额:$9.91万
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财政年份:2001
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Molecular Studies of Human All
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批准号:6360394
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资助金额:$22.33万
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财政年份:2001
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依托单位:
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批准号:6785381
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资助金额:$26.45万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
TRAINING PROGRAM IN INVESTIGATIVE HEMATOLOGY
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批准号:6906461
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项目类别:
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资助金额:$4.95万
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财政年份:2001
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依托单位:
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批准号:7280300
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资助金额:$26.28万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
Training Program in Investigative Hematology
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批准号:7486791
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项目类别:
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资助金额:$26.28万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
Molecular Studies of Human All
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批准号:6604226
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项目类别:
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资助金额:$22.51万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
Training Program in Investigative Hematology
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批准号:7067054
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项目类别:
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资助金额:$26.77万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
Molecular Studies of Human All
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批准号:6751585
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项目类别:
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资助金额:$22.6万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
Training Program in Investigative Hematology
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批准号:7668485
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项目类别:
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资助金额:$11.5万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
Molecular Studies of Human All
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批准号:6515197
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项目类别:
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资助金额:$22.32万
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财政年份:2001
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负责人:LINDA M BOXER
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依托单位:
CONTROL OF C-MYC TRANSCRIPTION IN AGGRESSIVE LYMPHOMAS
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批准号:6102161
-
项目类别:
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资助金额:$21.01万
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财政年份:1999
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负责人:LINDA M BOXER
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依托单位:
CONTROL OF C-MYC TRANSCRIPTION IN AGGRESSIVE LYMPHOMAS
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批准号:6269176
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项目类别:
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资助金额:$25.98万
-
财政年份:1998
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负责人:LINDA M BOXER
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依托单位:
CONTROL OF C-MYC TRANSCRIPTION IN AGGRESSIVE LYMPHOMAS
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批准号:6236697
-
项目类别:
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资助金额:$25.1万
-
财政年份:1997
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负责人:LINDA M BOXER
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依托单位:
REGULATION OF EXPRESSION OF C-MYB IN LEUKEMIAS
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批准号:2010192
-
项目类别:
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资助金额:$17.78万
-
财政年份:1996
-
负责人:LINDA M BOXER
-
依托单位:
REGULATION OF EXPRESSION OF C-MYB IN LEUKEMIAS
-
批准号:6173286
-
项目类别:
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资助金额:$19.55万
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财政年份:1996
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负责人:LINDA M BOXER
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依托单位:
REGULATION OF EXPRESSION OF C-MYB IN LEUKEMIAS
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批准号:2733270
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项目类别:
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资助金额:$19.07万
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财政年份:1996
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负责人:LINDA M BOXER
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依托单位:
CONTROL OF C MYC TRANSCRIPTION IN HIGH GRADE LYMPHOMAS
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批准号:2330957
-
项目类别:
-
资助金额:$17.87万
-
财政年份:1996
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负责人:LINDA M BOXER
-
依托单位:
CONTROL OF MYC TRANSCRIPTION IN HIGH GRADE LYMPHOMA
-
批准号:6263170
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项目类别:
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资助金额:$24.57万
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财政年份:1996
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负责人:LINDA M BOXER
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依托单位:
海外基金