Function of the Adenovirus E1B Oncogene
腺病毒 E1B 癌基因的功能
基本信息
- 批准号:6785973
- 负责人:
- 金额:$ 30.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-01-01 至 2006-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdenoviridaeBCL2 gene /proteinBax gene /proteinapoptosiscysteine endopeptidasescytochrome ccytokine receptorshost organism interactionlaboratory mousemicroorganism culturemitochondrianucleaseoncogenesoncoproteinsp53 gene /proteintumor necrosis factor alphaviral carcinogenesisvirus geneticsvirus proteinvirus replication
项目摘要
DESCRIPTION (provided by applicant): The human DNA tumor virus adenovirus
replicates productively in human cells and transforms primary rodent epithelial
cells. Integral to these activities is the deregulation of cell cycle control
and the inhibition of programmed cell death (apoptosis) by the viral oncogenes
E1A and E1B. E1A induces S-phase, which is required for replication of viral
DNA and stimulation of cell proliferation in transformation. E1A also induces
apoptosis that it requires E1B to inhibit to sustain productive infection and
permit oncogenic transformation. E1A deregulates the cell cycle by binding to
and inhibiting negative regulators of cell growth, one of which is the
retinoblastoma tumor suppressor gene product (Rb). E1B encodes two proteins
that block apoptosis by binding to and inhibiting pro-apoptotic proteins: 55K
binds and inhibits the p53 tumor suppressor protein; 19K binds and inhibits Bax
and other related pro-apoptotic components of the apoptotic machinery. I
propose to extend these studies in two specific areas that center around the
mechanism of modulation of death receptor signaling by E1A and E1B during
infection of human cells, and the mechanism of inhibition of p53-dependent
apoptosis downstream of mitochondria by the E1B 19K protein in rodent cells.
Finally, mice mutant for known components on the apoptotic machinery will be
utilized to establish the requirement and ordering of these gene products in
cell death signaling pathways in viral infection and transformation. By
executing these aims we hope to illuminate novel mechanisms of cell death
regulation and how they relate to virus replication and the development of
cancer. Knowledge gained from this approach will be useful in the development
of new anti-viral and anti-cancer regimens.
描述(申请人提供):人类DNA肿瘤病毒腺病毒
在人类细胞中高效复制并转化为原代啮齿动物上皮
细胞。这些活动的一个组成部分是解除对细胞周期控制的管制
以及病毒癌基因对细胞程序性死亡(细胞凋亡)的抑制
E1A和E1B。E1a诱导病毒复制所需的S期
DNA和刺激细胞在转化中的增殖。E1a还诱导
它需要E1B来抑制细胞凋亡以维持生产性感染和
允许致癌转化。E1a通过结合细胞周期来解除对细胞周期的调控
抑制细胞生长的负面调节因素,其中之一是
视网膜母细胞瘤肿瘤抑制基因产物(Rb)。E1B编码两种蛋白质
通过结合和抑制促凋亡蛋白来阻断细胞凋亡:55k
结合并抑制P53抑癌蛋白;19K结合并抑制Bax
以及凋亡机制中其他相关的促凋亡成分。我
建议将这些研究扩展到两个特定领域,主要围绕
E1a和E1B对死亡受体信号的调控机制
人细胞感染及其抑制P53依赖的机制
啮齿动物细胞中E1B 19K蛋白诱导线粒体下游的细胞凋亡。
最后,突变的小鼠的已知成分上的凋亡机制将是
用来确定这些基因产物的需求和排序
病毒感染和转化中的细胞死亡信号通路。通过
为了实现这些目标,我们希望阐明细胞死亡的新机制
监管以及它们与病毒复制和发展的关系
癌症。从这种方法中获得的知识将在开发中有用
新的抗病毒和抗癌疗法。
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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Eileen P. White其他文献
Eileen P. White的其他文献
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{{ truncateString('Eileen P. White', 18)}}的其他基金
(Diversity supplement to R01CA188096) Targeting autophagaphy in hereditary breast cancer
(R01CA188096 的多样性补充)针对遗传性乳腺癌的自噬
- 批准号:
9392413 - 财政年份:2015
- 资助金额:
$ 30.34万 - 项目类别: