Role of the Paf complex for the control of transcription by Drosophila Myc

Paf 复合物在果蝇 Myc 转录控制中的作用

• 批准号: 161793803
• 负责人: Professor Dr. Peter Gallant
• 金额: --
• 依托单位: Lehrstuhl für Biochemie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/161793803?language=en
• 关键词: Role; Paf; complex; control; transcription

Myc proto-oncoproteins are essential regulators of normal development and they play a major role in human cancer. They function as transcription factors that activate or repress a large number of different genes. However, the mechanism by which Myc controls the expression of its targets is not fully understood. To identify physiologically relevant transcriptional co-factors for Myc, and thereby decipher Myc’s mechanism of transactivation, we have conducted a pilot RNAi screen in Drosophila S2 cells. This screen resulted in the identification of several components of the Paf (“Polymerase II Associated Factor”) complex, and of other proteins known to interact with Paf. In preliminary experiments we demonstrated that the Paf complex is important for controlling Myc’s targets in S2 cells and Myc’s biological activities in vivo, and that the subunit Atu / Leo1 physically interacts with Myc. This application now proposes to characterize the interaction between Myc and the Paf complex (plus associated proteins), and to describe the molecular basis for their effect on transcription. In addition, we want to extend the screen for Myc cofactors to the full Drosophila genome, to obtain a complete list of the factors that normally control the activity of Myc.

Myc原癌蛋白是正常发育的重要调节因子，它们在人类癌症中起主要作用。它们作为转录因子发挥作用，激活或抑制大量不同的基因。然而，Myc控制其靶点表达的机制尚未完全了解。为了鉴定Myc的生理相关转录辅因子，从而破译Myc的反式激活机制，我们在果蝇S2细胞中进行了试验性RNAi筛选。该筛选导致鉴定了Paf（“聚合酶II相关因子”）复合物的几种组分，以及已知与Paf相互作用的其他蛋白质。在初步的实验中，我们证明了Paf复合物对于控制Myc在S2细胞中的靶点和Myc在体内的生物活性是重要的，并且亚基Atu /Leo 1与Myc物理相互作用。本申请现在提出表征Myc和Paf复合物（加上相关蛋白）之间的相互作用，并描述它们对转录的影响的分子基础。此外，我们希望将Myc辅因子的筛选扩展到整个果蝇基因组，以获得通常控制Myc活性的因子的完整列表。

项目成果

Drosophila Mbm Is a Nucleolar Myc and Casein Kinase 2 Target Required for Ribosome Biogenesis and Cell Growth of Central Brain Neuroblasts

• DOI: 10.1128/mcb.00658-13
• 发表时间: 2014-05-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Hovhanyan, Anna;Herter, Eva K.;Raabe, Thomas
• 通讯作者: Raabe, Thomas