Dissecting the regulatory roles of 14-3-3zeta on the adipogenic transcriptional program

脂肪细胞或脂肪细胞的生长是一个复杂的过程，涉及一个复杂的蛋白质网络。这些蛋白质需要出现在正确的位置和时间，但目前还不清楚脂肪细胞内是什么因素协调了这些蛋白质的作用。分子支架是可能的候选者，因为它们能够帮助蛋白质相互连接，并将它们保持在细胞的不同区域。在此之前，我发现一种叫做14-3-3的分子支架是脂肪细胞发育所必需的。没有14-3-3的老鼠非常瘦，脂肪也更少。另一方面，当喂食富含脂肪的食物时，每个细胞中14-3-3数量增加的老鼠变得更胖。除了这些控制脂肪量的作用外，14-3-3如何控制脂肪细胞生长的具体机制还需要进一步研究。14-3-3和该蛋白家族的其他成员是独特的，因为它们能够与多种蛋白质组连接，这表明它们可能通过多种途径和机制控制脂肪细胞的生长。因此，这项提议的目标是探索和定义这些途径，以便更好地了解脂肪细胞是如何形成的。为了更好地了解14-3-3在脂肪细胞生长中的作用，我们将利用CRISPR-Cas9技术制作一个新的细胞模型，在细胞中插入一个修改版本的14-3-3。这将允许简单而干净地提取14-3-3，以便了解它可能控制的基因类型，以及它可能接触、连接和影响的蛋白质的识别。我预计这些拟议的研究将确定参与脂肪细胞生长的新参与者。除了其他研究脂肪细胞发育的研究人员外，这项工作还有可能应用于不同研究领域的其他细胞类型。拟议研究的结果将增加我们对不同类型细胞如何发育的理解，并将揭示蛋白质在细胞中的作用是如何协调的。此外，从这些研究中获得的知识可以应用于开发受体脂增加影响的新疗法，如肥胖症、心脏病和糖尿病。

The growth of a fat cell, or adipocyte, is a complex process that involves a complicated network of proteins. These proteins need to be in the right place and time, but it is not well known what factors within the fat cell coordinate the actions of these proteins. Molecular scaffolds are possible candidates because of their abilities to help proteins connect with one another and to keep them in different areas of a cell. Previously, I have found that one molecular scaffold called 14-3-3 was required for fat cell development. Mice that did not have 14-3-3, were very lean and had less fat. On the other hand, mice that had increased amounts of 14-3-3 in every cell became fatter when fed a diet rich in fat. Despite these roles in controlling the amount of fat, the specific mechanisms of how 14-3-3 controls fat cell growth requires further investigation. 14-3-3 and other members of this protein family are unique because they are able to connect with a diverse group of proteins, and this suggests that they may control the growth of a fat cell through multiple pathways and mechanisms. Therefore, the goals of this proposal are to explore and define these pathways in order to better understand how fat cells are formed. To better understand the role of 14-3-3 in the growth of a fat cell, a new cell model will be made with CRISPR-Cas9 technology to insert a modified version of 14-3-3 in the cell. This will allow for the simple and clean extraction of 14-3-3 in order to see what types of genes it may control, as well as the identifies of proteins that it may touch, connect, and influence. I anticipate that these proposed studies will identify new players that are involved in the growth of fat cells. Aside from other researchers who study fat cell development, this work has the potential to be applied to other cell types across different fields of study. Results from the proposed studies will increase our understanding of how different types of cell develop and will reveal how the actions of proteins are coordinated in a cell. Furthermore, knowledge gained from these studies may be applied to the development of new therapies that are influenced by increases in body fat, such as obesity, heart disease, and diabetes.