Interactions of the SV40 Small T Antigen and PP2A in Human Cell Transformation
SV40 小 T 抗原和 PP2A 在人类细胞转化中的相互作用
基本信息
- 批准号:6989676
- 负责人:
- 金额:$ 12.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-04-27 至 2009-02-28
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We now understand neoplastic transformation to be the consequence of multiple acquired genetic alterations. These changes in aggregate confer the various phenotypes that constitute the clinical features of cancer. Although only rare human cancers derive from a viral etiology, the study of DNA tumor viruses that transform rodent and human cells has led to a greater understanding of the molecular events that program the malignant state. In particular, investigation of the viral oncoproteins specified by the Simian Virus 40 Early Region (SV40 ER) has revealed critical host cell pathways, whose perturbation play an essential role in the
experimental transformation of mammalian cells. Our recent work has re-investigated the roles of two SV40 ER oncoproteins, the large T antigen (T) and the small t antigen (t), in human cell transformation. Co-expression of these two oncoproteins, together with the telomerase catalytic subunit, hTERT, and an oncogenic version of the H-RAS oncoprotein, suffices to transform human cells. T inactivates two key tumor suppressor pathways by binding to the retinoblastoma protein (pRB) and p53. The ability of t to transform human cells requires interactions with specific subunits of the heterotrimeric protein phosphatase 2A (PP2A), an abundant family of serine-threonine phosphatases. In this application, we propose to use molecular biological, genetic, and biochemical approaches to investigate the molecular interactions that lead to human
cell transformation by t. Investigating the consequences of the interaction of t with PP2A will identify new pathways critical for cancer development as well as novel targets for cancer therapeutics.
我们现在知道肿瘤转化是多种获得性遗传改变的结果。这些变化总体上赋予了构成癌症临床特征的各种表型。虽然只有罕见的人类癌症源于病毒病因,但对转化啮齿动物和人类细胞的DNA肿瘤病毒的研究使人们对编程恶性状态的分子事件有了更深入的了解。特别地,对由猿猴病毒40早期区域(SV 40 ER)指定的病毒癌蛋白的研究已经揭示了关键的宿主细胞途径,其扰动在病毒的免疫应答中起重要作用。
哺乳动物细胞的实验性转化。我们最近的工作重新研究了两个SV 40 ER癌蛋白,大T抗原(T)和小t抗原(t),在人类细胞转化中的作用。这两种癌蛋白与端粒酶催化亚单位hTERT和H-RAS癌蛋白的致癌形式一起的共表达足以转化人类细胞。T通过与视网膜母细胞瘤蛋白(pRB)和p53结合来灭活两个关键的肿瘤抑制途径。t转化人类细胞的能力需要与异源三聚体蛋白磷酸酶2A(PP 2A)的特定亚基相互作用,PP 2A是丝氨酸-苏氨酸磷酸酶的丰富家族。在这个应用中,我们建议使用分子生物学,遗传学和生物化学方法来研究导致人类疾病的分子相互作用。
细胞转化T. 研究t与PP 2A相互作用的后果将确定癌症发展的新途径以及癌症治疗的新靶点。
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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WILLIAM C HAHN其他文献
WILLIAM C HAHN的其他文献
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{{ truncateString('WILLIAM C HAHN', 18)}}的其他基金
Development of p300/CBP histone acetyltransferase inhibitors for oncogene-driven cancers
开发用于癌基因驱动癌症的 p300/CBP 组蛋白乙酰转移酶抑制剂
- 批准号:
10344246 - 财政年份:2022
- 资助金额:
$ 12.82万 - 项目类别:
Development and implementation of multiplex methods to understand the biology and heterogeneity of patient-derived cancer models
开发和实施多重方法来了解源自患者的癌症模型的生物学和异质性
- 批准号:
10186722 - 财政年份:2020
- 资助金额:
$ 12.82万 - 项目类别:
Development and implementation of multiplex methods to understand the biology and heterogeneity of patient-derived cancer models
开发和实施多重方法来了解源自患者的癌症模型的生物学和异质性
- 批准号:
10458506 - 财政年份:2020
- 资助金额:
$ 12.82万 - 项目类别:
PROJECT 4: Interrogating PP2A Signaling in Human Cancers
项目 4:探究人类癌症中的 PP2A 信号传导
- 批准号:
10227785 - 财政年份:2017
- 资助金额:
$ 12.82万 - 项目类别:
The Dana-Farber Cancer Institute Cancer Target Discovery and Development Center
丹娜—法伯癌症研究所癌症靶标发现和开发中心
- 批准号:
10190844 - 财政年份:2013
- 资助金额:
$ 12.82万 - 项目类别:
Regulation and Function of Telomerase in Human Cells
人体细胞端粒酶的调节和功能
- 批准号:
7268675 - 财政年份:2004
- 资助金额:
$ 12.82万 - 项目类别:
Regulation and Function of Telomerase in Human Cells
人体细胞端粒酶的调节和功能
- 批准号:
7100941 - 财政年份:2004
- 资助金额:
$ 12.82万 - 项目类别:
Regulation and Function of Telomerase in Human Cells
人体细胞端粒酶的调节和功能
- 批准号:
6819379 - 财政年份:2004
- 资助金额:
$ 12.82万 - 项目类别:
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