Regulation of the cdk inhibitor, p27 Regulation des cdk inhibitor, p27

cdk 抑制剂的调节，第 27 页 cdk 抑制剂的调节，第 27 页

• 批准号: 5224632
• 负责人: Professor Dr. Martin Eilers
• 金额: --
• 依托单位: Lehrstuhl für Biochemie und Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1995
• 资助国家: 德国
• 起止时间: 1994-12-31 至 2001-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5224632?language=en
• 关键词: Regulation; cdk; inhibitor; p27; des

The proposal aims at elucidating two aspects of regulation of the cell cycle inhibitor, p27kip1. First, we have identified a nucleoporin, mNup2, which interacts with p27 in a two-hybrid assay and in vitro. Using a loss-of-interaction screen, we have identified a specific point mutant of p27 that fails to interact with Nup2. In vivo, this mutant is not correctly localised in the nucleus but accumulates in the Cytosol. We now want to understand the functional implications of this interaction during the cell cycle. Second, we aim at understanding the negative regulation of p27 by Myc. We have found that Myc-induced inactivation of p27 is mediated by cyclin D2. The promoter of the cyclin D2 gene is repressed by Mad proteins and derepressed by a direct interaction with Myc/Max complexes. We now need to fully understand the role of cyclin D2 in cell cycle control and transformation by Myc.

该提案旨在阐明细胞周期抑制因子p27kip1的两个方面的调控。首先，我们已经确定了一种核孔蛋白mNup2，它在双杂交实验和体外实验中与p27相互作用。使用失去相互作用的屏幕，我们已经确定了p27的一个特定的点突变，它无法与Nup2相互作用。在体内，这个突变体没有正确地定位在细胞核中，而是在胞浆中积累。我们现在想要了解这种相互作用在细胞周期中的功能含义。第二，我们旨在了解Myc对p27的负调控。我们发现Myc诱导的p27失活是由细胞周期蛋白D2介导的。细胞周期蛋白D2基因的启动子受Mad蛋白的抑制，并通过与Myc/Max复合体的直接相互作用而去抑制。我们现在需要充分了解细胞周期蛋白D2在细胞周期调控和Myc转化中的作用。