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

J Cell Sci. 2015 Jun 15;128(12):2219-28. doi: 10.1242/jcs.168922. Epub 2015 May 1.

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.

Keywords: Amino acid sensing; Autophagy; GATOR complex; SEA complex; TORC1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Expression Regulation, Fungal*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Stress, Physiological*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • Transcription Factors