VIRAL ONCOPROTEIN ACTIVATION IN AIDS-RELATED TUMORS
艾滋病相关肿瘤中病毒癌蛋白的激活
基本信息
- 批准号:6175245
- 负责人:
- 金额:$ 60.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-09-17 至 2004-06-30
- 项目状态:已结题
- 来源:
- 关键词:AIDS AIDS related neoplasm /cancer apoptosis cell line gene induction /repression gene targeting genetic mapping genetic promoter element genetic transcription genetically modified animals laboratory mouse neoplastic transformation oncoproteins tissue /cell culture transcription factor tumor suppressor genes virus protein yeast two hybrid system
项目摘要
DESCRIPTION: (Adapted from Applicant's Abstract) Tumor viruses, such as KSHV
and EBV, are responsible for the majority of AIDS-related malignancies,
including Kaposi's sarcoma and CNS lymphoma. Many tumor viruses share the
ability to directly or indirectly inhibit p 53 and pRB tumor suppressor
pathways. KSHV vIRF and EBV EBNA2 oncoproteins share a third common feature of
inhibiting interferon signaling which may contribute to cell transformation.
These investigators have found that vIRF and EBNA2, like adenovirus E1A, bind
the transscriptional coadaptor p300 involved in interferon and
apoptosis-related transcription. VIRF, EBNA2, and EIA induce the cMYC oncogene
promotor in a p300 regulated manner through an interferon-responsive element
and cMYC induction is required for vIRF-induced cell transformation. This
effect is mediated by an undiscovered transcriptional factor, provisionally
called PBF-X, may have general importance for the dysregulation of cMYC in both
infectious and non-infectious cancers. This is a collaborative research effort
designed to bring together two research groups to systematically examine the
effects of p300 binding by vIRF and EBNA2 on MYC induction and apoptotic
pathway inhibition. This will be achieved by mapping functional domains of vIRF
and EBNA2, and by fine mapping the response element sequences in the cMYC
promoter. The effects of p300 binding by EBNA3 and vIRF on p53-dependent and
independent apoptotic transcriptional responses will be examined using
p53-temperature sensitive mutant cells. Mechanistic studies (e.g. using protein
synthesis inhibition and dominant negative inhibitors) will broadly define the
pathway for cMYC induction and the contributing role of p300. The identity of
PBF-X will be sought from among eight known transcription factors (IRFs1-7 ,
and Blimp-1) and new candidates will be identified from yeast one- and
two-hybrid studies. After PBF-X is identified, knockout mice will be generated
for physiologic studies of the this transcriptonal factor. PBF-X is p potential
tumor suppressor candidate and LOH and chromosomal breakpoint data will be
examinded for mutations involving this locus. A pilot study of tumors,
particularly non-Burkitt's NHL with germline cMYC will be examined for PBF-X
mutations or LOH to test whether this transcription factor plays a role in
human tumorigenesis. These studies will lead to novel approaches in the control
of EBV and KSHV-related malignancies in AIDS patients.
描述:(改编自申请人摘要)肿瘤病毒,如KSHV
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('YUAN CHANG', 18)}}的其他基金
Role of a Novel Mitotic 4E-BP1 Protein Isoform in Cellular Transformation
新型有丝分裂 4E-BP1 蛋白亚型在细胞转化中的作用
- 批准号:
10582605 - 财政年份:2019
- 资助金额:
$ 60.75万 - 项目类别:
Role of a Novel Mitotic 4E-BP1 Protein Isoform in Cellular Transformation
新型有丝分裂 4E-BP1 蛋白亚型在细胞转化中的作用
- 批准号:
10372091 - 财政年份:2019
- 资助金额:
$ 60.75万 - 项目类别:
Role of a Novel Mitotic 4E-BP1 Protein Isoform in Cellular Transformation
新型有丝分裂 4E-BP1 蛋白亚型在细胞转化中的作用
- 批准号:
9765651 - 财政年份:2019
- 资助金额:
$ 60.75万 - 项目类别:
Transcriptomic and Proteomic Approaches to Discovering Viral Causes for Human Hem
转录组学和蛋白质组学方法发现人类血汗病的病毒原因
- 批准号:
8534746 - 财政年份:2012
- 资助金额:
$ 60.75万 - 项目类别:
Transcriptomic and Proteomic Approaches to Discovering Viral Causes for Human Hem
转录组学和蛋白质组学方法发现人类血汗病的病毒原因
- 批准号:
8383177 - 财政年份:2012
- 资助金额:
$ 60.75万 - 项目类别:
Transcriptomic and Proteomic Approaches to Discovering Viral Causes for Human Hem
转录组学和蛋白质组学方法发现人类血汗病的病毒原因
- 批准号:
8682795 - 财政年份:2012
- 资助金额:
$ 60.75万 - 项目类别:
VIRAL ONCOPROTEIN ACTIVATION IN AIDS RELATED TUMORS
艾滋病相关肿瘤中的病毒癌蛋白激活
- 批准号:
6017629 - 财政年份:1999
- 资助金额:
$ 60.75万 - 项目类别:
VIRAL ONCOPROTEIN ACTIVATION IN AIDS-RELATED TUMORS
艾滋病相关肿瘤中病毒癌蛋白的激活
- 批准号:
6377531 - 财政年份:1999
- 资助金额:
$ 60.75万 - 项目类别:
VIRAL ONCOPROTEIN ACTIVATION IN AIDS-RELATED TUMORS
艾滋病相关肿瘤中病毒癌蛋白的激活
- 批准号:
6661928 - 财政年份:1999
- 资助金额:
$ 60.75万 - 项目类别:
VIRAL ONCOPROTEIN ACTIVATION IN AIDS-RELATED TUMORS
艾滋病相关肿瘤中病毒癌蛋白的激活
- 批准号:
6514203 - 财政年份:1999
- 资助金额:
$ 60.75万 - 项目类别: