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.

该建议旨在阐明细胞周期抑制剂调节的两个方面P27KIP1。首先，我们已经确定了一种核孔蛋白MNUP2，该核孔蛋白在两个杂交测定中与P27相互作用和体外。使用相互作用损失屏幕，我们确定了未与NUP2相互作用的P27的特定点突变体。在体内，该突变体未正确定位在细胞核中，而是在细胞质中积聚。现在，我们想了解细胞周期中这种相互作用的功能含义。其次，我们旨在了解MYC对P27的负面调节。我们发现MYC诱导的p27失活是由细胞周期蛋白D2介导的。 Cyclin D2基因的启动子被MAD蛋白抑制，并通过与MYC/MAX复合物的直接相互作用消除。现在，我们需要充分了解Cyclin D2在MYC中的细胞周期控制和转化中的作用。