mTOR-what does it do?
mTOR-what does it do?
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DOI：
10.1016/j.transproceed.2008.10.009
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发表时间：
2008-12-01
影响因子：
0.9
通讯作者：
Hall, M N
中科院分区：
文献类型：
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作者：
Hall, M N
雷帕霉素靶蛋白（TOR）是一种高度保守的丝氨酸/苏氨酸激酶，它根据营养物质、生长因子、细胞能量和应激情况来控制细胞生长和代谢。TOR最初在酵母中被发现，在所有真核生物中都保守存在，包括植物、线虫、果蝇和哺乳动物。TOR的发现使我们对细胞生长的思考方式发生了根本性的改变。它不是一个在构建模块（营养物质）可用时就会自发发生的过程，而是一个由TOR依赖的信号通路控制的高度调控的、可塑性的过程。TOR存在于两种结构和功能不同的多蛋白复合物中，即TORC1和TORC2。这两种TOR复合物，就像TOR本身一样，是高度保守的。哺乳动物TORC1（mTORC1）对雷帕霉素敏感，包含mTOR、raptor和mLST8。酵母和哺乳动物中的TORC1通过调节几种细胞过程，包括翻译、转录、核糖体生物发生、营养物质运输和自噬，来介导细胞生长的时间控制。mTORC2对雷帕霉素不敏感，包含mTOR、rictor、mSIN1、PRR5和mLST8。酵母和哺乳动物中的TORC2通过调节肌动蛋白细胞骨架来介导细胞生长的空间控制。因此，这两种TOR复合物构成了一个在真核生物进化过程中保守的原始信号网络，以控制细胞生长的基本过程。作为细胞生长的核心调控因子，TOR在发育和衰老过程中起着关键作用，并且与癌症、心血管疾病、肥胖症和糖尿病等疾病有关。现在的挑战是了解mTOR信号在多细胞生物中协调和整合整体身体生长的作用。
Target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. TOR, which was originally discovered in yeast, is conserved in all eukaryotes including plants, worms, flies, and mammals. The discovery of TOR led to a fundamental change in how we think about cell growth. It is not a spontaneous process that just happens when building blocks (nutrients) are available, but rather a highly regulated, plastic process controlled by TOR-dependent signaling pathways. TOR is found in 2 structurally and functionally distinct multiprotein complexes, TORC1 and TORC2. The 2 TOR complexes, like TOR itself, are highly conserved. Mammalian TORC1 (mTORC1) is rapamycin sensitive and contains mTOR, raptor, and mLST8. TORC1 in yeast and mammals mediates temporal control of cell growth by regulating several cellular processes, including translation, transcription, ribosome biogenesis, nutrient transport, and autophagy. mTORC2 is rapamycin insensitive and contains mTOR, rictor, mSIN1, PRR5, and mLST8. TORC2 in yeast and mammals mediates spatial control of cell growth by regulating the actin cytoskeleton. Thus, the 2 TOR complexes constitute an ancestral signaling network conserved throughout eukaryotic evolution to control the fundamental process of cell growth. As a central controller of cell growth, TOR plays a key role in development and aging and has been implicated in disorders such as cancer, cardiovascular disease, obesity, and diabetes. The challenge now is to understand the role of mTOR signaling to coordinate and integrate overall body growth in multicellular organisms.