Dokudovskaya Svetlana, Rout Michael P
CNRS UMR 8126, Université Paris-Sud 11, Institut Gustave Roussy, 114, rue Edouard Vaillant, 94805, Villejuif, France
Laboratory of Cellular and Structural Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
J Cell Sci. 2015 Jun 15;128(12):2219-28. doi: 10.1242/jcs.168922. Epub 2015 May 1.
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.
细胞不断适应各种环境变化和压力。细胞内营养物质和压力水平反馈以控制新陈代谢和生长的方式极其复杂，这并不奇怪，因为对环境的“盛宴或饥荒、松弛或压力”状态做出高度敏感和快速的反应是任何生物体的核心目标。高度保守的雷帕霉素靶蛋白复合物1（TORC1）控制真核细胞的生长并对包括营养物质、激素和压力在内的多种信号作出反应，在自噬调节中起关键作用。最近，人们对该途径中在TORC1上游起作用的因素给予了很多关注。在本评论中，我们重点关注一种主要的、新发现的TORC1上游调节因子——多蛋白SEA复合物，也称为GATOR。我们描述了酵母复合物及其哺乳动物同源物的结构和功能特征，以及它们在TORC1途径调节和TORC1非依赖性过程中的作用。我们还将概述GATOR失调在癌症和其他疾病中的后果。
