SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

ABSTRACT 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. Summary: The multiprotein SEA/GATOR complex is a major upstream regulator of TORC1. This Commentary describes its structural and functional features, and provides an overview of the consequences of its deregulation in cancer.

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