Role of Miz1 in the Atr/Chk1 signalling pathway and in Myc-induced apoptosis

Miz1 在 Atr/Chk1 信号通路和 Myc 诱导的细胞凋亡中的作用

• 批准号: 5422428
• 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: Research Units
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5422428?language=en
• 关键词: Role; Miz1; Atr; Chk1; signalling

The proto-oncogene c-myc plays a key role in the genesis of a wide variety of human tumours. Understanding how c-myc acts in tumorigenesis requires an understanding of its biochemistry and the protein/protein interactions through which Myc affects cell physiology. c-myc encodes a transcription factor (Myc) that can both activate and repress transcription. A heterodimeric complex of Myc with a partner protein, Max, mediates transcriptional activation by Myc. Repression by Myc is mediated by distinct protein complexes; the best characterized is a trimeric protein complex, which contains Myc, Max, and the zinc finger protein Miz1. We do not understand mechanistically how Myc can both activate and repress transcription. We have recently obtained evidence that two known co-factors of Myc, the hexameric ATPases Tip48 and Tip49, repress transcription through Myc and Miz1. We propose to follow the mechanistic clues provided by these findings. Second, our recent work on transcriptional activation by Myc has defined specific pathways of activation and has provided evidence for a functional role of mediator and p-TEFB complexes in Myc-mediat ed gene activation. We therefore propose to identify the underlying biochemical interactions and test their role in activation and repression.

原癌基因c-myc在多种人类肿瘤的发生中起关键作用。了解c-myc在肿瘤发生中的作用需要了解其生物化学和Myc影响细胞生理学的蛋白质/蛋白质相互作用。c-myc编码一种既能激活又能抑制转录的转录因子（Myc）。Myc与伴侣蛋白Max的异二聚体复合物介导Myc的转录激活。Myc的抑制是由不同的蛋白质复合物介导的;最好的特征是三聚体蛋白质复合物，其中含有Myc，Max和锌指蛋白Miz 1。我们不知道Myc如何既能激活又能抑制转录。我们最近获得的证据表明，Myc的两个已知的辅因子，六聚体ATP酶Tip 48和Tip 49，通过Myc和Miz 1抑制转录。我们建议遵循这些发现提供的机制线索。其次，我们最近的工作转录激活Myc定义了特定的激活途径，并提供了证据的功能作用的介质和p-TEFB复合物的Myc介导的艾德基因激活。因此，我们建议确定潜在的生化相互作用，并测试它们在激活和抑制中的作用。