The role of TCTP in regulating adiponectin signaling

TCTP 在调节脂联素信号传导中的作用

基本信息

批准号：
9012095
负责人：
Lily Q Dong
金额：
$ 34.03万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9012095
关键词：
Adaptor Signaling Protein Adipose tissue Affect Binding Binding Proteins Cardiovascular Diseases Cells Complex Complications of Diabetes Mellitus Data Development Diet Down-Regulation Energy Metabolism Fatty Liver Fibrosis Functional disorder Health Hepatic Hepatocyte Human Impairment Inflammation Insulin Insulin Resistance Knock-out Knockout Mice Laboratories Lead Leucine Zippers Liver Messenger RNA Metabolic Metabolic Diseases Molecular Mus Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity PH Domain PTB Domain Pathway interactions Patients Phosphorylation Physiological Pioglitazone Play Prevention strategy Protein Isoforms Proteins Reducing diet Regulation Resistance Role Signal Transduction TPT1 gene Testing Therapeutic Thermogenesis Time Tissues Yeasts Yin-Yang adiponectin base cDNA Library glucose metabolism glucose production impaired glucose tolerance improved in vivo insulin sensitivity insulin sensitizing drugs insulin signaling lipid metabolism novel novel therapeutic intervention novel therapeutics obesity treatment overexpression prevent protein function receptor scaffold screening transcription factor yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Adiponectin has been well established as an insulin sensitizer to suppress glucose production and regulate hepatic lipid metabolism. However, the molecular mechanisms underlying adiponectin action remain largely unknown. Our laboratory identified for the first time an adiponectin receptor interactive protein, APPL1, which plays an essential role in adiponectin signaling. Subsequently, we showed that APPL2, an isoform of APPL1, acts as integrated Yin-Yang regulatory machinery with APPL1 to regulate adiponectin signaling in cells. To elucidate the mechanisms by which APPL isoforms regulate adiponectin signaling, we screened a yeast two-hybrid cDNA library using APPL2 as bait. This screening led to identification of TCTP as a binding protein that interacts with APPL isoforms. Based on our preliminary studies, we hypothesize that TCTP is a key regulator of adiponectin signaling in the liver and its interaction with APPL isoforms may provide a mechanism underlying obesity-induced down-regulation of adiponectin signaling. Impairment of adiponectin signaling together with reduced level of adiponectin in obesity and type 2 diabetes play important roles in development of insulin resistance. Understanding the mechanisms underlying TCTP-regulated adiponectin signaling may lead to identification of novel and effective therapeutic strategies for the prevention and treatment of metabolic disorders.

描述（由申请人提供）：脂联素已被广泛认为是一种抑制葡萄糖产生和调节肝脏脂质代谢的胰岛素增敏剂，然而，脂联素作用的分子机制仍然很大程度上未知。 , APPL1 在脂联素信号传导中发挥重要作用随后，我们证明 APPL2（APPL1 的同种型）发挥整合作用。阴阳调节机制与 APPL1 调节细胞内脂联素信号传导为了阐明 APPL 亚型调节脂联素信号传导的机制，我们使用 APPL2 作为诱饵筛选了酵母双杂交 cDNA 文库。根据我们的初步研究，TCTP 是肝脏脂联素信号传导及其相互作用的关键调节因子。 APPL 亚型可能提供肥胖引起的脂联素信号下调的机制。脂联素信号传导受损以及肥胖和 2 型糖尿病中脂联素水平的降低在了解 TCTP 调节的机制中发挥着重要作用。脂联素信号传导可能导致确定预防和治疗代谢紊乱的新颖且有效的治疗策略。