Mechanistic insights into the periodic control of transcription in the mammalian cell cycle

对哺乳动物细胞周期中转录周期性控制的机制见解

基本信息

批准号：
BB/M000036/1
负责人：
Andrew Sharrocks
金额：
$ 58.17万
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：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FM000036%2F1
关键词：
Mechanistic insights into periodic control

项目摘要

All of us develop into complex human beings containing millions of cells from a single cell created by fertilization of an egg. To transit from this single cell state, cells must continually divide into two cells, and in doing so pass a copy of their genetic blueprint (ie their DNA) to the new cells. This process is generally referred to as cell division. It is therefore critically important to understand the fundamental mechanisms that control this process. Conversely, as we age, cells become incapable of division and become "senescent". This creates a problem as we can no longer generate new cells to replace old or damaged cells. Conversely, hyperactivation of cell division leads to cancer. Indeed, cancer is a disease caused by the malfunction of "normal cells" in your body, and one of these malfunctions involves the onset of cell division. If this process goes unchecked, large masses of cells develop which accumulate more damage, and ultimately give rise to tumours. Thus understanding this critical process of cell division in normal cells and ultimately how this goes wrong in cancers is vitally important. This project aims to understand how one key regulator, FOXM1, works to control cell division. The abundance of this regulator is increased in cancer cells but is decreased in ageing cells, placing it at the nexus of control of these two important processes. FOXM1 does not work alone but has partners which help it to decode specific subparts of the genome in a process known as transcription. Here, we will study known partners and identify new partners for FOXM1. We will investigate how they work together to control cell division. This will provide a platform for establishing whether the mechanisms we uncover are relevant in the context of ageing or cancer and might lead to the development of therapeutic strategies.

我们所有人都会发展为复杂的人类，这些人是由卵受精产生的单个细胞中数百万个细胞的复杂人。要从单个细胞状态过渡，细胞必须不断分为两个细胞，然后将其遗传蓝图（即其DNA）的副本传递给新细胞。该过程通常称为细胞分裂。因此，了解控制这一过程的基本机制至关重要。相反，随着年龄的增长，细胞变得无法分裂并变得“衰老”。这会产生一个问题，因为我们无法再产生新的单元格来替代旧细胞或受损的单元。相反，细胞分裂的过度激活导致癌症。实际上，癌症是由您体内“正常细胞”故障引起的疾病，其中一种故障涉及细胞分裂的发作。如果该过程不受检查，则大量细胞会产生更多的损害，并最终导致肿瘤。因此，了解正常细胞中细胞分裂的这种关键过程以及最终在癌症中如何出现问题至关重要。该项目旨在了解一个关键调节器FOXM1如何控制细胞部门。癌细胞中这种调节剂的丰度增加，但在衰老细胞中降低，将其放置在这两个重要过程的控制层。 FOXM1不单独工作，但有合作伙伴可以帮助其在称为转录的过程中解码基因组的特定子部分。在这里，我们将研究已知合作伙伴，并确定FOXM1的新合作伙伴。我们将研究它们如何共同控制细胞分裂。这将提供一个平台，以确定我们发现的机制是否在衰老或癌症的背景下是否相关，并可能导致治疗策略的发展。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deregulation of the FOXM1 target gene network and its coregulatory partners in oesophageal adenocarcinoma.

DOI：
10.1186/s12943-015-0339-8
发表时间：
2015-03-26
期刊：
Molecular cancer
影响因子：
37.3
作者：
Wiseman EF;Chen X;Han N;Webber A;Ji Z;Sharrocks AD;Ang YS
通讯作者：
Ang YS

Forkhead box K2 modulates epirubicin and paclitaxel sensitivity through FOXO3a in breast cancer.

DOI：
10.1038/oncsis.2015.26
发表时间：
2015-09-07
期刊：
Oncogenesis
影响因子：
6.2
作者：
Nestal de Moraes G;Khongkow P;Gong C;Yao S;Gomes AR;Ji Z;Kandola N;Delbue D;Man EP;Khoo US;Sharrocks AD;Lam EW
通讯作者：
Lam EW