MECHANISMS OF REPRESSION BY THE RETINOBLASTOMA PROTEIN

视网膜母细胞瘤蛋白的抑制机制

• 批准号: 6173198
• 负责人: Steven Jay Weintraub
• 金额: $ 27.36万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-05 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173198
• 关键词: cell cycle; cell differentiation; cell growth regulation; chemical binding; crosslink; gene deletion mutation; gene expression; genetic promoter element; genetic regulation; genetic transcription; intermolecular interaction; molecular cloning; molecular oncology; neoplasm /cancer genetics; neoplastic growth; nucleic acid sequence; radiotracer; retinoblastoma protein; tissue /cell culture; transcription factor; transfection; tumor suppressor genes

DESCRIPTION (Adapted from applicant's abstract and specific aims): Retinoblastoma protein (Rb) function appears to be essential in the differentiation of airway epithelium as well as several other tissues. Conversely, it has recently been suggested that dysregulation of the Rb signal transduction pathway, either through mutation of Rb or aberrant function of another component of the pathway, occurs in all human malignancies. Therefore, studies of the role of Rb in the cell should lead to a further understanding of the processes of both cellular differentiation and malignant transformation. The investigators have previously shown that the Rb is a transcriptional repressor that is likely to control cellular proliferation and differentiation by regulating the expression of cell cycle genes. Rb is recruited to promoters through an interaction with E2F, a transcription factor (TF) known to bind to the promoters of several cell cycle genes and, once it is tethered to a promoter by E2F, Rb can interact simultaneously with E2F and surrounding TFs. The specific aims are to: 1) characterize the interaction between Rb and transcription factors; and 2) determine how Rb blocks interaction between transcription factors and the basal transcription complex.

描述（改编自申请人的抽象和具体目标）： 视网膜母细胞瘤蛋白 (Rb) 的功能似乎在 气道上皮以及其他几种组织的分化。 相反，最近有人提出，Rb 的失调 信号转导途径，通过 Rb 突变或异常 该途径的另一个组成部分的功能，发生在所有人类中 恶性肿瘤。 因此，研究 Rb 在细胞中的作用应该导致 进一步了解细胞分化的过程 和恶变。 研究人员此前已表明 Rb 是一种转录抑制因子，可能控制细胞 通过调节细胞周期的表达来增殖和分化 基因。 Rb 通过与 E2F 的相互作用被招募到启动子中， 已知与多个细胞的启动子结合的转录因子 (TF) 循环基因，一旦通过 E2F 连接到启动子，Rb 就可以相互作用 与 E2F 和周围的 TF 同时进行。 具体目标是：1） 表征 Rb 和转录因子之间的相互作用；和 2) 确定 Rb 如何阻断转录因子和 基础转录复合体。