Post-transcriptional regulation of gene expression by the Y-box factor ZONAB and cell survival

Y-box 因子 ZONAB 对基因表达的转录后调控和细胞存活

基本信息

批准号：
BB/H002294/1
负责人：
Karl Matter
金额：
$ 52.03万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH002294%2F1
关键词：
Post transcriptional regulation gene expression

项目摘要

Epithelia are continuous layers of cells that delineate our tissues and organs. Individual epithelial cells interact with each other via molecular complexes that mediate adhesion but also function as sensors that transmit information about the environment, such as the presence or absence of neighbouring cells, to the cell interior. Integrity of epithelia is important for our organs to function normally and to protect us from our environment. For example, breaches in epithelial layers such as the skin or in the lining of the intestine can lead to serious infections. Epithelial cells thus need molecular mechanisms that ensure proper responses to environmental and cellular factors that would otherwise lead to cell death and tissue damage. This proposal focuses on such a mechanism that is based on a protein that regulates expression of genes. Genes are part of the genome in the nucleus of cells, and encode the proteins that make up our cells and tissues. Genes are first transcribed into an mRNA, a messenger molecule that carries the information to the cellular machinery that synthesizes the proteins. Expression of genes can thus be regulated at different levels: transcription to mRNA, transport and stability of mRNA, and protein synthesis. Our experiments focus on a new mechanism by which epithelial cells respond to stress conditions to regulate the stability of mRNA and/or protein synthesis. This mechanism is important for cell survival as inactivation results in cell death in response to stress. The main component of this mechanism is a molecule that is regulated by adhesion complexes between cells as well as regulatory pathways known to be important for cellular responses. Our aims are to identity the molecular mechanisms by which this central component binds to mRNA and how this is stimulated by different stress conditions. We also want to determine which cellular components are directly affected as well as the importance of such components for cell survival. Understanding how cells respond to stress and how they ensure survival is important for our understanding of how tissues and organs form and maintain themselves. Many diseases such as infections and cancer as well as environmental toxins cause cellular stress and understanding how cells respond will help us to design new therapies. In some cases, cell death is the goal of a therapy, as it is in the case of chemotherapy to fight cancer. Hence, identifying mechanisms that keep cells alive will also aid the development of approaches to increase the efficiencies of existing therapies by targeting such mechanisms in combination with chemotherapy.

上皮是描绘我们组织和器官的细胞的连续层。单个上皮细胞通过介导粘附的分子复合物相互相互作用，并且还充当传递有关环境信息的传感器，例如存在或不存在相邻细胞的信息，以传递到细胞内部。上皮的完整性对于我们的器官正常运作并保护我们免受环境至关重要。例如，诸如皮肤或肠壁上的上皮层中的漏洞会导致严重的感染。因此，上皮细胞需要分子机制，以确保对环境和细胞因子的适当反应，否则会导致细胞死亡和组织损伤。该建议的重点是基于调节基因表达的蛋白质的机制。基因是细胞核中基因组的一部分，并编码构成我们细胞和组织的蛋白质。首先将基因转录为mRNA，mRNA是一种将信息带到合成蛋白质的细胞机械的信使分子。因此，基因的表达可以在不同的水平下调节：对mRNA的转录，mRNA的转运和稳定性和蛋白质合成。我们的实验集中在一种新机制上，上皮细胞对应力条件的反应以调节mRNA和/或蛋白质合成的稳定性。这种机制对于细胞存活很重要，因为失活导致细胞死亡响应压力。该机制的主要成分是一个分子，该分子受细胞之间的粘附复合物以及已知对于细胞反应很重要的调节途径调节。我们的目的是识别该中心成分与mRNA结合的分子机制，以及如何通过不同的应力条件刺激这种机制。我们还想确定哪些细胞成分受到直接影响，以及此类成分对细胞存活的重要性。了解细胞对压力的反应以及它们如何确保生存对于我们对组织和器官如何形成和维护自己的理解很重要。许多疾病，例如感染和癌症以及环境毒素会导致细胞压力，并了解细胞的反应将有助于我们设计新的疗法。在某些情况下，细胞死亡是治疗的目的，就像在化学疗法的情况下对抗癌症。因此，识别保持细胞生存的机制也将有助于开发方法，通过将这种机制与化学疗法结合使用，以提高现有疗法的效率。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family.

DOI：
10.1186/1471-2121-10-95
发表时间：
2009-12-22
期刊：
BMC cell biology
影响因子：
0
作者：
Steed E;Rodrigues NT;Balda MS;Matter K
通讯作者：
Matter K

Lowe Syndrome protein OCRL1 supports maturation of polarized epithelial cells.

DOI：
10.1371/journal.pone.0024044
发表时间：
2011
期刊：
PloS one
影响因子：
3.7
作者：
Grieve AG;Daniels RD;Sanchez-Heras E;Hayes MJ;Moss SE;Matter K;Lowe M;Levine TP
通讯作者：
Levine TP

Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex.