自然杂志 ›› 2018, Vol. 40 ›› Issue (4): 297-304.doi: 10.3969/j.issn.0253-9608.2018.04.010

• 自然科学史 • 上一篇    下一篇

雷帕霉素靶蛋白:细胞生长调控之门

郭晓强   

  1. 北京大学 深圳医院, 广东 深圳 518036
  • 收稿日期:2017-12-13 出版日期:2018-08-25 发布日期:2018-09-03
  • 作者简介:通信作者,研究方向:肾癌发生机制,主要涉及组蛋白修修饰为主的表观遗传学、低氧信号通路与mTOR信号通路。E-mail: xiaoqiangguo123@163.com

TOR (target of rapamycin): the gate of cell growth

GUO Xiaoqiang   

  1. Shenzhen Hospital, Peking University, Shenzhen 518036, Guangdong Province, China
  • Received:2017-12-13 Online:2018-08-25 Published:2018-09-03

摘要:

雷帕霉素(rapamycin)是一种大环内酯类化合物,最初于1972年由塞加尔从复活岛吸水链霉菌中成功分离。1991年,霍尔首次从酵母中鉴定出雷帕霉素靶蛋白(TOR),从而打开细胞生长和发育机制研究之门。TOR或mTOR是一种重要的分子整合器,可感知来自生长因子、激素、氨基酸和氧状态等的信号,并通过调节下游因子而影响蛋白质、脂类和核苷酸等的合成。TOR/mTOR信号通路在生长和代谢中发挥着重要作用,它的调节紊乱可导致癌症、衰老和糖尿病等多种疾病的发生。雷帕霉素及类似物(rapalogs)已被美国FDA批准应用于预防器官移植排斥反应和治疗肾细胞癌和神经内分泌肿瘤等癌症。文章介绍雷帕霉素和TOR的发现历程以及TOR信号通路的生理作用、机制和临床应用等。

Abstract:

t Rapamycin is a macrolide compound which was isolated from samples of Streptomyces hygroscopicus found on Easter Island of Rapa Nui by Surendra Sehgal in 1972. TOR (target of rapamycin) was first identified in Saccharomyces cerevisiae by Michael Hall in 1991, which opened the doors to unravel fundamental mechanisms of cell growth and development. TOR or mTOR (mechanistic TOR) is an important molecular integrator that senses signals arising from growth factors, hormones, amino acids and oxygen status, and then integrates these signals to regulate metabolic pathways involving the synthesis of proteins, lipids, and
nucleotides. TOR/mTOR signaling plays a central role in the control of growth and metabolism. Its dysregulation can contribute to a variety of diseases including cancer, aging and diabetes. Rapalogs (rapamycin and its analogs) had been approved by the US FDA for prevention of transplant rejection, treatment of certain cancers including renal cell carcinoma and neuroendocrine tumors. Here, the discovery process of rapamycin and TOR, the physiological role, mechanism and clinical application of TOR signaling pathway are introduced.