Cytoplasmic and transcriptional control of Hippo signaling

Hippo 信号传导的细胞质和转录控制

基本信息

批准号：
10063875
负责人：
Kenneth H Moberg
金额：
$ 28.61万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063875
关键词：
Address Adhesives Adult Apical Area Binding Binding Proteins Biological Assay Biology Cadherins Cancerous Cell Nucleus Cell division Cell membrane Cells ChIP-seq Chromatin Complement Complex Cues Cytoplasm DNA Data Data Set Development Drosophila genus Drosophila melanogaster Early Endosome Ecdysone Elements Elephants Endosomes Epithelial Epithelial Attachment Epithelial Cells Estrogens Gene Expression Genes Genetic Genetic Transcription Genome Genomics Goals Gonadal Steroid Hormones Growth Growth Factor Histones Homologous Gene Hormone Receptor Hormones Human Knowledge Lead Learning Light Link Lysosomes Malignant Neoplasms Maps Membrane Messenger RNA Molecular Mus Nuclear Nuclear Hormone Receptors Nutrient Occupations Organ Organism Output PH Domain Pathologic Pathway interactions Pattern Phosphatidylinositols Phospholipids Phosphorylation Positioning Attribute Protein-Serine-Threonine Kinases Proteins Proteomics Publishing Receptor Signaling Reporter Role Scallop Sequence-Specific DNA Binding Protein Signal Transduction Site Structure Surface Techniques Testing Testosterone Time Tissues Transcription Coactivator Transcriptional Regulation Translating Tumor Suppressor Proteins Vertebrates Vesicle Work base cell growth chromatin protein comparative experimental study extracellular fly genome-wide histone methyltransferase human disease imaginal disc in vivo late endosome prevent programs promoter protein protein interaction recruit regenerative response stem stem cell genes synergism trafficking transcriptional intermediary factor 1 tumor

项目摘要

Project Summary/Abstract The overall goal of this proposal is to understand how organisms as diverse as humans and the fruit flies use the same molecules to determine how large their organs will grow. The specific focus of this application is a protein that controls expression of genes that in turn encode for proteins that promote growth. In flies this `pro- growth' factor is called Yorkie and in our cells it is called Yap1, however it performs the same job in both species. When Yorkie/Yap1 is `active' in cells, it tells the cells to grow and divide, and thus generates many new cells. This makes tissues larger since they have more cells, but it can also lead to the growth of a cancerous tumor. We know a bit about how Yorkie/Yap1 become `active' but not enough to reliably predict when and where this happens, or how it promotes cancer when it becomes `active' all the time. We have found three other proteins that physically bind to Yorkie: RhoGAP15B, Taiman, and Bonus, and we think they may be key to understanding when and where Yorkie gets activated. RhoGAP15B has the ability to bind cell membranes, so we hypothesize that it may interact with Yorkie and tether it to specific kinds of membranes in epithelial cells. Yorkie is known to localize to a set of membranes in the cellular cytoplasm called `endosomes', and RhoGAP15B may be the factor that takes it there. Taiman and Bonus are proteins that are found in the nucleus, where the DNA is housed, and get `activated' by the fly equivalent of the human sex hormones estrogen and testosterone. We think that when these hormones `activate' Taiman and Bonus that they also activate Yorkie, and that this is an important way cells receive signals to turn `on' genes in the DNA that tell the cells to grow and divide. Our experiments will address each of these ideas: Does RhoGAP15B help tether Yorkie to cell membrane and why does this matter? Do Taiman and Yorkie cooperate in binding to DNA and selecting which genes get expressed from the DNA in the nucleus? Is Bonus involved in helping Yorkie activate genes that are responsible for cell growth and division? Although we use flies to study these ideas, we remain confident that much of what we learn will teach us about how all of the proteins work in our cells.

项目概要/摘要该提案的总体目标是了解人类和果蝇等多种生物体如何利用相同的分子来决定它们的器官会生长多大。该应用程序的具体重点是控制基因表达的蛋白质，而基因又编码促进生长的蛋白质。在苍蝇中这个“亲” 生长因子称为 Yorkie，在我们的细胞中称为 Yap1，但它在两种细胞中执行相同的工作物种。当 Yorkie/Yap1 在细胞中“活跃”时，它会告诉细胞生长和分裂，从而产生许多新细胞。这使得组织变得更大，因为它们有更多的细胞，但它也可能导致细胞的生长癌性肿瘤。我们对 Yorkie/Yap1 如何变得“活跃”有一些了解，但还不足以可靠地预测这种情况发生的时间和地点，或者当它一直“活跃”时它如何促进癌症。我们还发现了另外三种与约克犬物理结合的蛋白质：RhoGAP15B、Taiman 和 Bonus，以及我们认为它们可能是了解约克夏何时何地被激活的关键。 RhoGAP15B有能力结合细胞膜，因此我们假设它可能与约克犬相互作用并将其与特定种类的上皮细胞中的膜。已知约克夏定位于细胞质中的一组膜称为“内体”，RhoGAP15B 可能是将其带到那里的因子。 Taiman 和 Bonus 是蛋白质存在于 DNA 所在的细胞核中，并被相当于人类的苍蝇“激活” 性激素雌激素和睾酮。我们认为，当这些激素“激活”Taiman 和 Bonus 它们还激活约克犬，这是细胞接收信号以“打开”基因的重要方式 DNA 告诉细胞生长和分裂。我们的实验将解决这些想法中的每一个： RhoGAP15B 有助于将约克夏犬束缚在细胞膜上，为什么这很重要？泰曼和约克有合作吗与 DNA 结合并选择哪些基因从细胞核中的 DNA 中表达？是否涉及奖金帮助约克激活负责细胞生长和分裂的基因？虽然我们用苍蝇来研究这些想法，我们仍然相信，我们学到的大部分知识将告诉我们所有蛋白质是如何工作的我们的细胞。

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）

NDR kinase tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development.

DOI：
10.1093/g3journal/jkad013
发表时间：
2023-03-09
期刊：
G3-GENES GENOMES GENETICS
影响因子：
2.6
作者：
Hudson, Joshua;Paul, Sayantanee;Veraksa, Alexey;Ghabrial, Amin;Harvey, Kieran F.;Poon, Carole
通讯作者：
Poon, Carole