Thinking globally and acting locally with TOR
Thinking globally and acting locally with TOR
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DOI：
10.1016/j.ceb.2006.09.005
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发表时间：
2006-12-01
影响因子：
7.5
通讯作者：
Neufeld, Thomas P.
中科院分区：
文献类型：
--
作者：
Arsham, Andrew M.;Neufeld, Thomas P.
雷帕霉素靶蛋白（TOR）通路调节核糖体生物合成、蛋白质合成、营养物质输入、自噬和细胞周期进程。经过30年的集中关注，TOR如何控制这些过程现在才开始被理解。最近的进展已经确定了广泛的TOR输入，包括氨基酸，氧，ATP和生长因子，以及促进其对TOR作用的调节蛋白。这些蛋白质包括AMPK、Rheb和肿瘤抑制因子LKB 1、p53和Tsc 1/2。直到最近才意识到，TOR存在于两种具有不同调节作用的不同信号复合物中，其中只有一种是雷帕霉素敏感的，从而开辟了一条新的途径来研究TOR功能。最后，TOR似乎通过促进器官系统之间的通信来调节进食行为，因此涉及葡萄糖和脂肪稳态的调节，并且可能涉及糖尿病和肥胖症。因此，TOR的功能是在细胞和有机体水平上协调允许生长的输入和促进生长的输出。
The target of rapamycin (TOR) pathway regulates ribosome biogenesis, protein synthesis, nutrient import, autophagy and cell cycle progression. After 30 years of concentrated attention, how TOR controls these processes is only now beginning to be understood. Recent advances have identified a wide array of TOR inputs, including amino acids, oxygen, ATP and growth factors, as well the regulatory proteins that facilitate their effects on TOR. Such proteins include AMPK, Rheb and the tumor suppressors LKB1, p53, and Tsc1/2. It has only recently been appreciated that TOR resides in two distinct signaling complexes with differing regulatory roles, only one of which is rapamycin-sensitive, thus opening a new avenue of inquiry into TOR function. Finally, TOR appears to regulate feeding behavior by facilitating communication between organ systems, and is thus implicated in the regulation of glucose and fat homeostasis, and possibly diabetes and obesity. TOR thus functions to coordinate growth-permitting inputs with growth-promoting outputs on both a cellular and an organismal level.