Sudarsanam Sucha, Johnson Dale E
Emiliem Inc, Emeryville, CA 94608-1903, USA.
Curr Opin Drug Discov Devel. 2010 Jan;13(1):31-40.
TOR (target of rapamycin) is a serine-threonine protein kinase that is conserved across a diverse range of species from fungi to mammals. The signaling pathway that is anchored by TOR is also conserved across species. In mammals, mTOR integrates growth factor, amino acid, nutrient and energy sensing signals, and thus plays a major role in cell growth and proliferation, protein synthesis and autophagy. As a result of the pivotal role of mTOR in signaling, the aberrant regulation of mTOR has been implicated in several disease processes, including cancer, diabetes, ocular diseases and neurodegenerative disorders, as well as in lifespan extension. More recently, rapamycin (sirolimus) analogs that antagonize the mTOR signaling pathway have been approved for the treatment of several cancers. This review describes some recent advances in the understanding of mTOR signaling, with an emphasis on the functional consequences of mTOR inhibition and therapeutic intervention strategies.
雷帕霉素靶蛋白（TOR）是一种丝氨酸 - 苏氨酸蛋白激酶，在从真菌到哺乳动物等多种物种中都高度保守。由TOR锚定的信号通路在物种间也具有保守性。在哺乳动物中，mTOR整合生长因子、氨基酸、营养和能量感知信号，因此在细胞生长与增殖、蛋白质合成及自噬过程中发挥主要作用。由于mTOR在信号传导中起关键作用，mTOR的异常调节与多种疾病进程相关，包括癌症、糖尿病、眼部疾病和神经退行性疾病，以及寿命延长。最近，拮抗mTOR信号通路的雷帕霉素（西罗莫司）类似物已被批准用于治疗多种癌症。本综述描述了对mTOR信号传导理解的一些最新进展，重点在于mTOR抑制的功能后果和治疗干预策略。
