Cell cycle regulation by ubiquitin ligases

泛素连接酶的细胞周期调节

基本信息

批准号：
7995625
负责人：
David Paul Toczyski
金额：
$ 8.56万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-20 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7995625
关键词：
Adaptor Signaling Protein Alleles Architecture Binding Biochemistry Biology Catalytic Domain Cell Cycle Cell Cycle Progression Cell Cycle Regulation Cell division Cell physiology Cellular biology Characteristics Chimeric Proteins Chromosomes Complex Data Docking Enzymatic Biochemistry Enzymes F-Box Proteins Genetic Genetic Transcription Glucose Glycogen Synthase Kinases Goals In Vitro Libraries Life Ligase Malignant Neoplasms Mediating Metabolic Methodology Methods Microscopy Modeling Mutation Names Nature Nutrient Pathway interactions Phenotype Phosphoproteins Phosphotransferases Post-Translational Protein Processing Proteins Proteome Proteomics Regulation Role Screening procedure Series Set protein Signal Pathway Specificity Structure Substrate Specificity System Techniques Testing Ubiquitin Ubiquitin-mediated Proteolysis Pathway Ubiquitination Ursidae Family Yeasts c-myc Genes deprivation detection of nutrient dimer genome wide association study in vivo multicatalytic endopeptidase complex novel protein degradation public health relevance receptor research study response transcription factor tumor ubiquitin ligase

项目摘要

DESCRIPTION (provided by applicant): Rapid changes in cell physiology during cell cycle transitions or in response to changes in external conditions are often mediated by the degradation of regulatory molecules. These changes are typically directed by the modification of protein targets with chains of the small protein ubiquitin. Ubiquitinization is carried out by a series of three enzymes, sometimes referred to as E1, E2 and E3, which function in tandem to transfer ubiquitin to a substrate. Substrate specificity is usually mediated by the E3 complex, also called a ubiquitin ligase. The SCF and the APC represent two highly conserved multi-subunit ubiquitin ligases important for both cell cycle progression and the regulation of many aspects of cellular physiology. We will examine mechanisms of APC regulation, and also identify the substrates of these and other ubiquitin ligases using a comprehensive screening technique that we have recently developed. PUBLIC HEALTH RELEVANCE: Cancer is the result of uncontrolled cell division. In this proposal, we outline experiments that characterize proteins responsible for the regulation of cell division. In doing this, we can better understand how cancers arise and the characteristics of tumors that can be used to selectively target them.

描述（由申请人提供）：细胞周期转变期间或响应外部条件变化时细胞生理学的快速变化通常是由调节分子的降解介导的。这些变化通常是通过用小蛋白泛素链修饰蛋白质靶标来引导的。泛素化是由一系列三种酶（有时称为 E1、E2 和 E3）进行的，它们协同作用将泛素转移到底物上。底物特异性通常由 E3 复合物介导，也称为泛素连接酶。 SCF 和 APC 代表两种高度保守的多亚基泛素连接酶，对于细胞周期进程和细胞生理学许多方面的调节都很重要。我们将研究 APC 调节机制，并使用我们最近开发的综合筛选技术来鉴定这些和其他泛素连接酶的底物。公共卫生相关性：癌症是不受控制的细胞分裂的结果。在本提案中，我们概述了表征负责调节细胞分裂的蛋白质的实验。通过这样做，我们可以更好地了解癌症是如何产生的以及可用于选择性靶向它们的肿瘤的特征。