The role of PKC in chromatin structure and gene regulation

PKC 在染色质结构和基因调控中的作用

基本信息

批准号：
BB/H010858/1
负责人：
Andrew Sharrocks
金额：
$ 59.07万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH010858%2F1
关键词：
role PKC chromatin structure gene

项目摘要

Cells within multicellular organisms have developed mechanisms for sensing their local environment and responding in an appropriate manner. In particular, they need to respond to signals produced by other cells in the body or to environmental insults. Cells have developed signalling pathways to transmit signals from the cell periphery to the rest of the cell. One major destination for these pathways is the nucleus. Here the pathways target key molecular switches known as transcription factors. Through the modification of the transcription factors by a process known as phosphorylation, their activity is altered, and this changes their ability to unlock the genetic code and alter the expression of whole cohorts of genes. This project will investigate how one signalling pathway containing the important protein PKC functions in controlling the expression of genes in the cell. PKC is important as it directly senses the integrity of the cell surface. We will use yeast as a simple model organism as this is easily manipulatable. Importantly, PKC is conserved in humans so things that we learn in yeast can have immediate impacts on our understanding of human physiology and disease as exemplified by our previous work on different yeast signalling proteins. As PKC is a target which drug companies are developing drugs against, our findings are likely to have important implications for understanding how these drugs might act and hence help in directing their use in treating human ailments such as heart disease and cancer.

多细胞生物体内的细胞已经发展出感知局部环境并以适当方式做出反应的机制。特别是，它们需要对体内其他细胞产生的信号或环境侵害做出反应。细胞已经发展出信号传导途径，将信号从细胞外周传输到细胞的其余部分。这些途径的主要目的地之一是细胞核。此处，这些途径针对称为转录因子的关键分子开关。通过磷酸化过程对转录因子进行修饰，它们的活性被改变，这改变了它们解锁遗传密码和改变整个基因组表达的能力。该项目将研究包含重要蛋白 PKC 的信号通路如何在控制细胞中基因表达方面发挥作用。 PKC 很重要，因为它直接感知细胞表面的完整性。我们将使用酵母作为简单的模型生物，因为它易于操作。重要的是，PKC 在人类中是保守的，因此我们在酵母中学到的东西可以对我们对人类生理学和疾病的理解产生直接影响，正如我们之前对不同酵母信号蛋白的研究所证明的那样。由于 PKC 是制药公司开发药物的目标，我们的研究结果可能对了解这些药物如何发挥作用具有重要意义，从而有助于指导它们在治疗心脏病和癌症等人类疾病中的使用。