PROTEIN INTERACTIONS AND REPRESSION FUNCTION OF E1A

E1A 的蛋白质相互作用和抑制功能

• 批准号: 2700449
• 负责人: Elizabeth Moran
• 金额: $ 32.17万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2700449
• 关键词: Adenoviridae; DNA binding protein; enzyme activity; gene expression; helicase; intermolecular interaction; molecular cloning; protein structure function; tissue /cell culture; transcription factor; virus protein

DESCRIPTION: The E1A-associated protein, p300, is of major interest to cancer biologists because, as a direct target of the transforming functions of the adenovirus E1A gene, it is implicated in the regulation of both cell cycle specific and tissue specific gene expression. p300 is highly homologous to the CREB coactivator, CBP. CREB and CBP are the major mediators of the transcriptional response to cyclic AMP-responsive pathways. The relationship between p300 and CBP suggests that they perform, similar functions. Nevertheless, they are encoded by different genes, and preliminary clinical evidence indicates that specific metabolic disorders are linked with selective loss of CBP, indicating that p300 and CBP are not functionally redundant. The investigators identified a new 270 kilodalton product that is related to both p300 and CBP. p270 is particularly interesting because it exists in cells as a component of a tightly associated series of proteins. Moreover they have identified a prominent member of this complex as BRG1. The BRG1 protein product is a transcriptional activator, a regulator of gene expression pathways linked with the development and differentiation, and a putative DNA helicase. The p207/BRG1 complexes with this activity intact. The identification of this interaction should open the way to understanding a major part of the molecular mechanisms of action of the p300 and BRG1 families, two families of proteins that appear to be pivotal regulators of gene expression in pathways controlling cell proliferation and differentiation.

描述：E1a相关蛋白，p300，与 癌症生物学家因为，作为转化功能的直接靶点 在腺病毒E1a基因中，它与两个细胞的调节有关 周期特异性和组织特异性基因表达。P300是高度 与CREB共激活因子CBP同源。CREB和CBP是主要的 环状AMP反应途径转录反应的介体。 P300和CBP之间的关系表明，它们的表现相似 功能。然而，它们是由不同的基因编码的，并且 初步临床证据表明，特定的代谢紊乱 与CBP的选择性丢失有关，表明p300和CBP不是 功能上是多余的。调查人员发现了一种新的270千道尔顿 与P300和CBP都相关的产品。P270特别是 有趣的是，它作为紧密连接的组件存在于细胞中 相关的一系列蛋白质。此外，他们还确定了一个突出的 这个复合体的成员，被称为BRG1。BRG1蛋白产物是一种 转录激活因子--基因表达途径的调节因子 随着发育和分化，推测有一种DNA解旋酶。这个 具有这种活性的p207/BRG1复合体。这一点的认定 互动应该为理解 P300和BRG1家族的分子作用机制 这些蛋白质似乎是基因表达的关键调节因子 控制细胞增殖和分化的途径。