ADENOVIRUS E1A PROTEIN AND THE SWI/SNF COMPLEX

描述：（改编自研究者摘要）：腺病毒E1 A 蛋白质诱导培养物中细胞的永生化和转化， 因此是研究细胞转化的极好模型。E1a 结合包括视网膜母细胞瘤蛋白（Rb）在内的特异性细胞蛋白， p300/CBP蛋白通过改变染色质部分控制转录 结构E1 A抑制染色质重塑复合物的功能 SWI/SNF，其与Rb蛋白和可能的p300相互作用。具体目标1 建议定义和表征哺乳动物SWI/SNF复合体， 它在转录调控中的作用。将决定如何 复合物在转录水平抑制c-fos表达。结构性 伴随c-fos基因活性抑制的变化将是 特征，并将开发检测方法来测量物理关联 的SWI/SNF与特定的哺乳动物启动子在体内。研究将描述 E1 A对SWI/SNF过程的影响。具体目标2将使用酵母 遗传学方法来理解E1 A对SWI/SNF复合物的抑制。酵母 将鉴定与E1 A相互作用的蛋白质，并研究它们对E1 A的影响。 活动将被确定。类似的研究将在 哺乳动物细胞使用从酵母系统获得的信息。

DESCRIPTION:(Adapted from the Investigator's abstract): The adenovirus E1A protein induces imortalization and transformation of cells in culture and is therefore an excellent model for the study of cellular transformation. E1A binds specific cell proteins including the retinoblastoma protein (Rb) and p300/CBP proteins that control transcription, in part, by altering chromatin structure. E1A inhibits the function of the chromatin remodeling complex SWI/SNF, which interacts with Rb protein and possibly p300. Specific aim 1 proposes to define and characterize the mammalian SWI/SNF complex with respect to its role in regulation of transcription. It will be determined how the complex inhibits c-fos expression at the transcriptional level. The structural changes that accompany the inhibition of c-fos gene activity will be characterized, and assays will be developed to measure the physical association of SWI/SNF with specific mammalian promoters in vivo. Studies will characterize the effects of E1A on SWI/SNF processes. Specific aim 2 will use a yeast genetic approach to understand E1A inhibition of the SWI/SNF complex. The yeast proteins that interact with E1A will be identified and their influence on E1A activity will be determined. Similar studies will then be conducted in mammalian cells using the information gained from the yeast system.