Cell cycle control by the Myc/Max/Mad network: Regulation of Mad by cyclin E/CDK2 and identification and characterization of Mad1 target genes Zellzyklusregulation durch das Myc/Max/Mad Netzwerk: Regulation von Mad durch Cyclin E/CDK2 und Identifizierung

点击翻译按钮获取中文摘要

The proteins of the Myc/Max/Mad network play pivotal roles in the regulation of cell growth, differentiation and apoptosis. Myc/Max/Mad complexes are sequence-specific DNA binding proteins that function as transcriptional regulators. While the basic aspects of the function of Myc and its regulation are understood, it is not clear whether Mad1 proteins are regulated by any signaling and which are the target genes. Since we have found that the cyclin E/CDK2 kinase complex interferes with Mad1 inhibition of cell cycle progression we propose to study how this kinase affects Mad1 function. In particular we will ask whether cyclin E/CDK2 can modulate the Mad1-repressor complex. The second aim is to identify Mad1 target genes using an in vivo cross-linking approach. This will allow us to identify in vivo binding sites for Mad1 proteins and to clone the corresponding DNA. These DNA fragments can be used to identify associated genes which will then be characterized with a particular emphasis on the role of the encoded proteins in Mad1mediated inhibition of S phase progression.