SEA you later alli-GATOR - a dynamic regulator of the TORC1 stress response pathway
SEA you later alli-GATOR - a dynamic regulator of the TORC1 stress response pathway
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DOI：
10.1242/jcs.168922
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发表时间：
2015-06-15
影响因子：
4
通讯作者：
Rout, Michael P.
中科院分区：
文献类型：
--
作者：
Dokudovskaya, Svetlana;Rout, Michael P.
细胞不断适应各种环境变化和压力。不出所料，细胞中的营养和压力水平反馈以控制新陈代谢和生长的方式是极其复杂的，因为对其环境的“丰盛或饥荒、松弛或压力”状态做出非常敏感和迅速的反应是任何有机体的中心目标。雷帕霉素复合体1(TORC1)是一个高度保守的靶标，控制着真核细胞的生长和对包括营养物质、激素和应激在内的多种信号的响应，在自噬的调节中起着关键作用。最近，人们对该途径中作用于TORC1上游的因素给予了极大的关注。在这篇评论中，我们集中在TORC1的一个主要的，新发现的上游调节因子-多蛋白SEA复合体，也被称为GATOR。我们描述了酵母复合体及其哺乳动物同源物的结构和功能特征，以及它们参与调控TORC1途径和TORC1非依赖过程。我们还将概述鳄鱼放松管制对癌症和其他疾病的影响。
Cells constantly adapt to various environmental changes and stresses. The way in which nutrient and stress levels in a cell feed back to control metabolism and growth are, unsurprisingly, extremely complex, as responding with great sensitivity and speed to the 'feast or famine, slack or stress' status of its environment is a central goal for any organism. The highly conserved target of rapamycin complex 1 (TORC1) controls eukaryotic cell growth and response to a variety of signals, including nutrients, hormones and stresses, and plays the key role in the regulation of autophagy. A lot of attention has been paid recently to the factors in this pathway functioning upstream of TORC1. In this Commentary, we focus on a major, newly discovered upstream regulator of TORC1 - the multiprotein SEA complex, also known as GATOR. We describe the structural and functional features of the yeast complex and its mammalian homolog, and their involvement in the regulation of the TORC1 pathway and TORC1-independent processes. We will also provide an overview of the consequences of GATOR deregulation in cancer and other diseases.