TRANSCRIPTION CONTROL BY THE NUCLEAR ONCOPROTEIN, E1A
核癌蛋白 E1A 的转录控制
基本信息
- 批准号:3199778
- 负责人:
- 金额:$ 16.37万
- 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:1991-07-01 至 1994-06-30
- 项目状态:已结题
- 来源:
- 关键词:Adenoviridae DNA binding protein antibody binding proteins cell free system gene expression genetic transcription host organism interaction laboratory rabbit molecular cloning mutant oncoproteins phosphorylation protein sequence regulatory gene transcription factor viral carcinogenesis virus antigen virus genetics virus infection mechanism
项目摘要
The long term goal of this proposal is to elucidate the transcription
regulatory pathways that are also targets of oncogene action such as the
adenovirus ElA. Several oncogene products have been identified.
Determination of the biochemical functions of these oncogene products
will eventually elucidate the pathways that lead to transformation and
tumorigenesis. Evidence is accumulating that the majority of the
oncogene products are involved in the control of gene expression. This
proposal involves functional analysis Of ElA oncogene products with
regard to their effect on the activities on the cellular proteins such as
E2F, E4F and E2FBP. E2F and E4F are cellular transcription factors that
are involved in the control of the adenovirus early genes. E2FBP is an
E2F binding protein that modulates E2F activity by forming a complex with
E2F which in turn is regulated by ElA proteins.ElA dissociates E2F/E2FBP
complex requiring the domains 1 and 2 of ElA and these two domains are
also involved in the transformation function of this oncoprotein. Thus a
major focus of this proposal is biochemical characterization of E2FBP and
production of specific antisera against E2FBP which will help analyzing
the basis of ElA control. The SV40 T antigen and the HPV E7 protein
possess sequence homology with domains 1 and 2 of ElA and these two
oncoproteins also trans-activate adenovirus E2 promoter depending on the
E2F binding site. These two proteins will also be analyzed for their
ability to control E2F/E2FBP interaction. The other interest of this
proposal is to analyze the mechanism that control the DNA binding
activity of the ElA-regulated transcription factor E4F. Specific
reagents, like peptide antisera and cDNA clones, will be obtained using
the peptide sequence information. These reagents will be extremely
valuable in the studies of E4F regulation by phosphorylation as well as
by the adenovirus ElA gene products. The proposal also focuses on
identification of a cellular kinase that might be involved in the
regulation of E4F DNA binding activity.
这项建议的长期目标是阐明转录
调节途径也是致癌基因作用的靶点,例如
腺病毒ElA。 已经鉴定出几种癌基因产物。
这些癌基因产物的生化功能的测定
最终将阐明导致转化的途径,
肿瘤发生 越来越多的证据表明,
癌基因产物参与基因表达的控制。 这
建议涉及ElA癌基因产物的功能分析,
考虑到它们对细胞蛋白活性的影响,
E2 F、E4 F和E2 FBP。 E2 F和E4 F是细胞转录因子,
参与腺病毒早期基因的控制。 E2 FBP是一个
一种通过与E2 F形成复合物来调节E2 F活性的E2 F结合蛋白
E2 F又受ElA蛋白的调节,ElA使E2 F/E2 FBP解离
复合物需要ElA的结构域1和2,这两个结构域是
也参与这种癌蛋白的转化功能。 因此
该提案的主要重点是E2 FBP的生物化学表征,
生产针对E2 FBP的特异性抗血清,这将有助于分析
控制的基础。 SV 40 T抗原和HPV E7蛋白
与ElA的结构域1和2具有序列同源性,这两个结构域
癌蛋白也反式激活腺病毒E2启动子,这取决于
E2 F结合位点。 还将分析这两种蛋白质的
控制E2 F/E2 FBP相互作用的能力。 另一个有趣的是
建议分析控制DNA结合的机制
E1 A调节的转录因子E4 F的活性。 具体
将使用以下方法获得试剂,如肽抗血清和cDNA克隆,
肽序列信息。 这些试剂将非常
在E4 F通过磷酸化调节的研究中有价值,
腺病毒E1 A基因产物。 该提案还着重于
鉴定一种细胞激酶,其可能参与
E4 F DNA结合活性的调节。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Activation of the c-fos gene by the HPV16 oncoproteins depends upon the cAMP-response element at -60.
HPV16 癌蛋白对 c-fos 基因的激活取决于 -60 处的 cAMP 反应元件。
- DOI:
- 发表时间:1994
- 期刊:
- 影响因子:0
- 作者:Morosov,A;Phelps,WC;Raychaudhuri,P
- 通讯作者:Raychaudhuri,P
Identification of a 60-kilodalton Rb-binding protein, RBP60, that allows the Rb-E2F complex to bind DNA.
鉴定出 60 千道尔顿的 Rb 结合蛋白 RBP60,该蛋白允许 Rb-E2F 复合物结合 DNA。
- DOI:10.1128/mcb.12.10.4327-4333.1992
- 发表时间:1992
- 期刊:
- 影响因子:5.3
- 作者:Ray,SK;Arroyo,M;Bagchi,S;Raychaudhuri,P
- 通讯作者:Raychaudhuri,P
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