Regulation and function of the YAP transcription co-activator oncoprotein

YAP转录辅激活癌蛋白的调控和功能

基本信息

批准号：
8022881
负责人：
Kun-Liang Guan
金额：
$ 31.1万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-08 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8022881
关键词：
11q22 Apoptosis Cancer Cell Growth Regulation Cell Death Cell Proliferation Cell Proliferation Regulation Cell physiology Cells Contact Inhibition Cyclin E Data Development Drosophila genus Epithelial Gene Expression Gene Expression Regulation Gene Targeting Genetic Genetic Transcription Goals Homologous Gene Human Human Chromosomes Human Development Inhibition of Apoptosis Malignant Neoplasms Malignant neoplasm of liver Malignant neoplasm of prostate Mammalian Cell Mediating Mesenchymal MicroRNAs Molecular Mutation Neurofibromatosis 2 Oncogene Proteins Oncogenes Oncogenic Organ Size PRDM4 gene Pathway interactions Phosphorylation Inhibition Play Protein Kinase Proteins Regulation Role Signal Pathway Testing Tumor Suppressor Proteins Work cIAP1 protein member mutant novel protein function public health relevance response transcription factor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Regulation and function of the YAP transcription co-activator oncoprotein The yes-associated protein YAP is a potent transcription co-activator. Recent genetic studies have implicated YAP as a candidate oncogene in human chromosome 11q22 amplicon. Drosophila studies have established a novel tumor suppressor pathway Hippo that regulates both cell proliferation and apoptosis. Many components of the Hippo pathway are highly conserved. YAP is likely to be the major target inhibited by the Hippo pathway. YAP can functionally rescue yorkie (the Drosophila homolog of mammalian YAP) mutation in Drosophila. It has been suggested that the neurofibromatosis 2 (NF2) tumor suppressor is a component of the Hippo pathway acting upstream of YAP to inhibit YAP function. However, the Hippo pathway has not been investigated in mammalian cells. The long term goals of this project are to determine the function and regulation of the Hippo pathway in development of human cancers. Our preliminary data have shown that the Hippo-YAP pathway plays an essential role in cell contact inhibition and oncogenic transformation. Furthermore, YAP is highly elevated in human cancers, including prostate and liver cancers. The specific aims of this proposal are: 1. To identify and characterize YAP target transcription factors 2. To determine the function of YAP target transcription factors in cell contact inhibition, oncogenic transformation, and epithelial-mesenchymal transition 3. To determine the function of YAP-induced micro RNA Public Health Relevance: YAP is a transcription co-activator and oncogene highly elevated in human cancers. This proposal will study the molecular mechanism of YAP in tumorigenesis by promoting cell proliferation and inhibiting cell death.

描述（由申请人提供）：YAP转录共激活剂的调节和功能与是相关的蛋白质YAP是有效的转录共激活因子。最近的遗传研究已暗示了YAP作为人类染色体11q22扩增子中的候选癌基因。果蝇研究已经建立了一种新型的肿瘤抑制途径，可以调节细胞增殖和凋亡。河马途径的许多组成部分都是高度保守的。 YAP可能是河马途径抑制的主要目标。 YAP可以在果蝇中功能营救约克（哺乳动物YAP的果蝇同源物）。已经提出，神经纤维瘤病2（NF2）肿瘤抑制剂是hippo途径的组成部分，在YAP上游作用以抑制YAP功能。但是，尚未在哺乳动物细胞中研究河马途径。该项目的长期目标是确定人类癌症发展中河马途径的功能和调节。我们的初步数据表明，HIPPO-YAP途径在细胞接触抑制和致癌转化中起着至关重要的作用。此外，在包括前列腺和肝癌在内的人类癌症中，YAP高度升高。该提案的具体目的是： 1。识别和表征YAP目标转录因子 2。确定YAP目标转录因子在细胞接触抑制，致癌转化和上皮 - 间质转变中的功能 3。确定YAP诱导的微RNA的功能公共卫生相关性：YAP是人类癌症中高度升高的转录共同激活剂和癌基因。该建议将通过促进细胞增殖和抑制细胞死亡来研究肿瘤发生中YAP的分子机制。