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Whi2: a new player in amino acid sensing

Authors
  • Teng, Xinchen1, 2
  • Hardwick, J. Marie2
  • 1 Soochow University, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Suzhou, Jiangsu, 215123, China , Suzhou (China)
  • 2 Johns Hopkins University Bloomberg School of Public Health, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Baltimore, MD, 21205, USA , Baltimore (United States)
Type
Published Article
Journal
Current Genetics
Publisher
Springer-Verlag
Publication Date
Jan 30, 2019
Volume
65
Issue
3
Pages
701–709
Identifiers
DOI: 10.1007/s00294-018-00929-9
Source
Springer Nature
Keywords
License
Yellow

Abstract

A critical function of human, yeast, and bacterial cells is the ability to sense and respond to available nutrients such as glucose and amino acids. Cells must also detect declining nutrient levels to adequately prepare for starvation conditions by inhibiting cell growth and activating autophagy. The evolutionarily conserved protein complex TORC1 regulates these cellular responses to nutrients, and in particular to amino acid availability. Recently, we found that yeast Whi2 (Saccharomyces cerevisiae) and a human counterpart, KCTD11, that shares a conserved BTB structural domain, are required to suppress TORC1 activity under low amino acid conditions. Using yeast, the mechanisms were more readily dissected. Unexpectedly, Whi2 suppresses TORC1 activity independently of the well-known SEACIT–GTR pathway, analogous to the GATOR1–RAG pathway in mammals. Instead, Whi2 requires the plasma membrane-associated phosphatases Psr1 and Psr2, which were known to bind Whi2, although their role was unknown. Yeast WHI2 was previously reported to be involved in regulating several fundamental cellular processes including cell cycle arrest, general stress responses, the Ras–cAMP–PKA pathway, autophagy, and mitophagy, and to be frequently mutated in the yeast knockout collections and in genome evolution studies. Most of these observations are likely explained by the ability of Whi2 to inhibit TORC1. Thus, understanding the function of yeast Whi2 will provide deeper insights into the disease-related KCTD family proteins and the pathogenesis of plant and human fungal infections.

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