Bar-Peled Liron, Sabatini David M
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, MA 02142, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Cambridge MA 02142, USA.
Trends Cell Biol. 2014 Jul;24(7):400-6. doi: 10.1016/j.tcb.2014.03.003. Epub 2014 Mar 31.
The mechanistic target of rapamycin complex I (mTORC1) is a central regulator of cellular and organismal growth, and hyperactivation of this pathway is implicated in the pathogenesis of many human diseases including cancer and diabetes. mTORC1 promotes growth in response to the availability of nutrients, such as amino acids, which drive mTORC1 to the lysosomal surface, its site of activation. How amino acid levels are communicated to mTORC1 is only recently coming to light by the discovery of a lysosome-based signaling system composed of Rags (Ras-related GTPases) and Ragulator v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes. Increased understanding of this pathway will not only provide insight into growth control but also into the human pathologies triggered by its deregulation.
雷帕霉素复合物I（mTORC1）的机制靶点是细胞和机体生长的核心调节因子，该信号通路的过度激活与包括癌症和糖尿病在内的许多人类疾病的发病机制有关。mTORC1响应营养物质（如氨基酸）的可用性来促进生长，氨基酸会将mTORC1驱动到溶酶体表面，即其激活位点。氨基酸水平如何传递给mTORC1直到最近才通过发现一种基于溶酶体的信号系统而得以揭示，该系统由Rags（Ras相关GTP酶）和Ragulator v-ATP酶、GATOR（Rags的GAP活性）以及卵泡抑素（FLCN）复合物组成。对该信号通路的深入了解不仅将有助于深入了解生长控制，还将有助于深入了解由其失调引发的人类疾病。
