Analysis of the stress resistance functions of Prolyl Isomerase Pin1

脯氨酰异构酶Pin1的抗应激功能分析

基本信息

批准号：
16380225
负责人：
UCHIDA Takafumi
金额：
$ 10.53万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

We found that. Pin1 is a stress resistance protein that is related to cancer and Alzheimer's disease. Pin1 regulates the stability of an oncogene, c-myc. C-myc is degraded by ubiquitination. If myc is not degraded and remains in the cell, the cell becomes immortalized and develops to cancer cell. Therefore Pin1 functions to resist to the stress of tumor development. The mice without Pin1 and p53 developed thymoma, which is caused by over production of NIC, activated Notch1. Pin1 also suppresses the tumor signal of Notch1. In brains, Pin1 regulate the production of Amyloid beta from amyloid precursor protein. Pin1 binds to the phosphoThr668 and changes the conformation of the site cut by g-secretase. Production of amyloid beta is considered one of the most important events in the development of Alzheimer's disease. Our finding will be useful to diagnose and produce a drug for Alzheimer's disease. We also discovered that Pin1 activates Stat3 signal, which is related to inflammation and immunity. This is the other example showing that. Pint is a responder to the stress to the cell or body. We also found that. Pin1 suppresses the apoptosis caused by spinal cord injury. We guessed there are molecules that function like Pin1 in the body to suppress. The stress, and found Gas7 that has similar amino acid sequence to Pin T. The level of Gas7 is very low in the brains of the patients with Alzheimer's disease. We think Gas7 may be another stress responsive protein like Pin1.

我们发现。 PIN1是一种与癌症和阿尔茨海默氏病有关的应激性蛋白。 PIN1调节癌基因C-Myc的稳定性。 C-MYC因泛素化而降解。如果MYC没有降解并保留在细胞中，则细胞将永生化并发展为癌细胞。因此，PIN1的功能可以抵抗肿瘤发育的应力。没有PIN1和p53的小鼠出现了胸腺瘤，这是由于NIC过度生产而激活的Notch1引起的。 PIN1还抑制了Notch1的肿瘤信号。在大脑中，PIN1调节淀粉样蛋白蛋白质的淀粉样蛋白β的产生。 PIN1结合了磷脂668，并改变了通过G-分泌酶切割的位点的构象。淀粉样蛋白β的生产被认为是阿尔茨海默氏病发展中最重要的事件之一。我们的发现对于诊断和生产阿尔茨海默氏病的药物很有用。我们还发现PIN1激活与炎症和免疫有关的STAT3信号。这是显示这一点的另一个示例。品脱是对细胞或身体压力的响应者。我们还发现。 PIN1抑制脊髓损伤引起的凋亡。我们猜测，体内有像PIN1一样抑制的分子。应力，并发现具有与引脚T的氨基酸序列相似的气体。在阿尔茨海默氏病患者的大脑中，气体水平非常低。我们认为GAS7可能是诸如PIN1之类的另一种应力响应蛋白。