MOLECULAR GENETIC ANALYSIS OF A YEAST RB-LIKE PATHWAY

酵母 RB 样途径的分子遗传学分析

• 批准号: 3085979
• 负责人: RAYMUND S CUEVO
• 金额: $ 7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-20 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085979
• 关键词: DNA binding protein; Saccharomyces cerevisiae; Schizosaccharomyces pombe; fungal genetics; genetic transcription; molecular cloning; polymerase chain reaction; transcription factor; tumor suppressor genes; yeasts

The functional inactivation of tumor suppressor genes (anti-oncogenes) plays an important role in tumorigenesis. The inactivation of these genes is postulated to result in loss of responsiveness to growth inhibitory signals, allowing uncontrolled growth. One tumor-suppressor gene, the retinoblastoma (Rb) gene is thought to regulate cell growth by repressing the transcription of growth stimulatory genes, such as c-fos, and stimulating the transcription of growth inhibitory genes, such as TGFbeta via cis-acting DNA sequences called retinoblastoma control elements (RCE). Recent experimental evidence suggests that Rb functions to regulate transcription by forming inactive complexes with transcription factors. To enhance our understanding of Rb function, we have sought to identify an Rb-like pathway in yeast. Preliminary work has identified an RCE-specific binding protein of 200 kd (p2OO) from the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. This result suggests that a conserved transcriptional regulatory network may exist in both yeast and mammalian cells. Assuming that the yeast RCE-binding protein is structurally as well as functionally homologous to a mammalian RCE-binding factor, we propose to use yeast to facilitate the cloning of mammalian RCE-binding factors, as well as determine if a transcriptional regulatory pathway controlled by an Rb-like protein exists in yeast.

肿瘤抑制基因的功能失活（抗癌基因） 在肿瘤发生中起重要作用。 这些基因的失活 假设会导致对生长抑制的反应能力 信号，允许不受控制的增长。 一个肿瘤抑制基因， 视网膜母细胞瘤（RB）基因被认为可以通过抑制来调节细胞生长 生长刺激基因的转录，例如C-FOS和 刺激生长抑制基因的转录，例如TGFBETA 通过顺式作用DNA序列称为视网膜细胞瘤对照元件（RCE）。 最近的实验证据表明，RB功能可以调节 通过与转录因子形成非活性复合物的转录。 到 增强我们对RB功能的理解，我们试图确定 酵母中的RB状途径。 初步工作已经确定了RCE特定的 来自酵母菌的200 kD（P2OO）的结合蛋白 和酿酒酵母。 这个结果表明保守 酵母和哺乳动物的转录调节网络可能存在 细胞。 假设酵母RCE结合蛋白在结构上也是 作为功​​能与哺乳动物RCE结合因子同源的，我们建议 使用酵母促进哺乳动物RCE结合因子的克隆，作为 以及确定是否由一个转录调节途径控制 RB样蛋白存在于酵母中。