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

上皮是描绘我们的组织和器官的连续的细胞层。单个上皮细胞通过分子复合体相互作用，分子复合体不仅介导黏附，而且还起到传感器的作用，将有关环境的信息，如邻近细胞的存在或不存在，传递到细胞内部。上皮细胞的完整性对于我们的器官正常运作和保护我们免受环境的伤害是很重要的。例如，皮肤或肠道衬里等上皮层的破裂可能会导致严重的感染。因此，上皮细胞需要分子机制来确保对环境和细胞因素的适当反应，否则这些因素将导致细胞死亡和组织损伤。这项提议的重点是这样一种机制，它基于一种调节基因表达的蛋白质。基因是细胞核中基因组的一部分，它编码组成我们细胞和组织的蛋白质。基因首先被转录成信使分子，信使分子将信息传递给合成蛋白质的细胞机器。因此，基因的表达可以在不同的水平上进行调节：转录为信使核糖核酸，信使核糖核酸的运输和稳定性，以及蛋白质的合成。我们的实验着眼于一种新的机制，即上皮细胞通过对应激条件的反应来调节mRNA和/或蛋白质合成的稳定性。这一机制对细胞存活很重要，因为失活会导致细胞在应激反应中死亡。这一机制的主要组成部分是一种分子，它受细胞之间的黏附复合体以及已知对细胞反应重要的调节途径的调节。我们的目标是确定这个中心成分与mRNA结合的分子机制，以及不同的胁迫条件是如何刺激这一机制的。我们还想确定哪些细胞成分受到直接影响，以及这些成分对细胞生存的重要性。了解细胞如何对压力做出反应，以及它们如何确保生存，对于我们理解组织和器官如何形成和维持自己非常重要。许多疾病，如感染、癌症以及环境毒素，都会引起细胞压力，了解细胞如何反应将有助于我们设计新的治疗方法。在某些情况下，细胞死亡是治疗的目标，就像抗击癌症的化疗一样。因此，识别保持细胞存活的机制也将有助于开发方法，通过将这些机制与化疗相结合来提高现有疗法的效率。

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.