Regulation of Differentiation in Caulobacter

柄杆菌分化的调控

基本信息

批准号：
7642349
负责人：
LUCILLE SHAPIRO
金额：
$ 55.47万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7642349
关键词：
ATP phosphohydrolase Biogenesis Carbon Caulobacter Caulobacter crescentus Cell Cycle Cell Cycle Progression Cell Cycle Regulation Cell division Cell membrane Cells Clear Cell Complex Cytokinesis Development Environment Event Functional RNA Gene Cluster Genes Genetic Genetic Transcription Genome Goals Grant Individual Life Mediating Membrane Membrane Proteins Molecular Molecular Chaperones Operating System Organelles Organism Pattern Peptide Hydrolases Phase Phosphorylation Play Positioning Attribute Protein Dynamics Proteins Proteolysis Proteomics Regulation Regulation of Proteolysis Replication Initiation Replication Origin Research Personnel Role Signal Transduction Signaling Protein System Time Transcriptional Regulation Untranslated RNA Work cell cycle genetics daughter cell deprivation genetic regulatory protein programs promoter protein-histidine kinase response

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposal is to define the regulatory mechanisms that control the bacterial cell cycle and to understand how these mechanisms function within an integrated system. We have shown that the control of the Caulobacter crescentus cell cycle incorporates discrete transcription patterns, controlled proteolytic events that clear the cell of critical regulatory proteins at defined times in the cell cycle, and dynamic localization of polar phospho- signaling proteins that orchestrates the activity of cell cycle regulators. A transcriptional network governed by three global regulators (CtrA, GcrA, DnaA) that oscillate out of phase temporally and spatially has been shown to regulate the temporal expression of approximately 200 genes. This transcriptional network influences and is influenced by the subcellular organization of the cell and its progressive changes during the cell cycle. Cellular compartmentalization preceding cell division is a critical signal for the differential activation of specific proteolytic events in the daughter cells. The CIpXP protease, responsible for the timely degradation of the CtrA global regulator, must be localized at the cell pole with its CtrA substrate for this function. Further, the timing of CIpXP localization is controlled by signaling from the transiently localized CckA histidine kinase that also mediates the activation of CtrA at the correct time in the cell cycle, thus creating a robust transcriptional network. We will focus on identifying the factors responsible for protein localization and the dynamic regulation of the proteolytic mechanisms that play a fundamental role in cell cycle progression, and identifying the factors that contribute to and integrate cell cycle regulatory networks. In addition, because free living organisms must readily adapt to a changing environment, it is critical to understand how this regulatory circuitry works not only under optimal conditions, but also how it is re-programmed when the cell is challenged; and how, when conditions are favorable again, it begins anew. We will explore individual regulatory mechanisms in depth while determining how they function in an integrated system that operates in time and space to carry out the functions of a living cell.

描述（由申请人提供）：该提案的目的是定义控制细菌细胞周期的调节机制，并了解这些机制在集成系统中的作用。我们已经表明，对花椰菜齿状细胞周期的控制结合了离散的转录模式，受控的蛋白水解事件，这些事件清除了细胞周期中定义的时间的关键调节蛋白的细胞，以及极性磷酸信号传导蛋白的动态定位，这些蛋白质策划了细胞周期调节剂的活性。由三个全球调节剂（CTRA，GCRA，DNAA）控制的转录网络，该网络在时间和空间上振荡偶发，以调节大约200个基因的时间表达。该转录网络会影响细胞的亚细胞组织及其在细胞周期中的渐进变化影响。细胞分裂之前的细胞分区化是子细胞中特定蛋白水解事件的差异激活的关键信号。 CIPXP蛋白酶，负责CTRA全局调节剂及时降解的CIPXP蛋白酶，必须在细胞极定位，其CTRA底物为此功能。此外，CIPXP定位的时机通过瞬时局部CCKA组氨酸激酶的信号传导来控制，该激酶还介导了细胞周期中正确时间的CTRA激活，从而产生了强大的转录网络。我们将重点介绍负责蛋白质定位的因素以及在细胞周期进程中起着基本作用的蛋白水解机制的动态调节，并确定有助于和整合细胞周期调节网络的因素。此外，由于自由的生物体必须很容易适应不断变化的环境，因此必须了解该调节电路不仅在最佳条件下运作，而且在挑战细胞时如何重新编程。当条件再次有利时，它如何重新开始。我们将深入探讨单个调节机制，同时确定它们在在时空运行以执行活细胞功能的集成系统中的功能。