Target of rapamycin (TOR) in nutrient signaling and growth control.

Department of Molecular Biology and National Centers of Competence in Research and Frontiers in Genetics and Chemical Biology, University of Geneva, Geneva, CH-1211, Switzerland.
Genetics (Impact Factor: 4.87). 12/2011; 189(4):1177-201. DOI: 10.1534/genetics.111.133363
Source: PubMed

ABSTRACT TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Methylotrophic yeast Pichia pastoris has proved to be especially useful for production of various heterologous proteins. In biotechnology it is very important to maintain the balance between high levels of heterologous gene expression and cell viability. Decisive understanding of gene regulation mechanisms is essential for reaching this goal. In this study, we investigated the effect of different nitrogen sources and phosphate concentration in media on methanol utilization. It was shown that expression levels of main genes, which are involved in methanol utilization (MUT genes) and in functioning of peroxisomes (PEX genes), are maximal when ammonium sulphate is used as a nitrogen source. Expression of these genes is decreased in media with poor nitrogen sources, such as proline. Addition of rapamycin to the media completely removed repression of AOX1 promoter in media with proline, which allows proposing that Tor-kinase is involved in establishing of nitrogen regulation of this gene. It was also shown that MUT genes expression levels get higher, when the phosphate concentration in media is increased.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the last few years extensive studies have linked the activity of mTORC1 to lysosomal function. These observations propose an intriguing integration of cellular catabolism, sustained by lysosomes, with anabolic processes, largely controlled by mTORC1. Interestingly, lysosomal function directly affects mTORC1 activity and is regulated by ZKSCAN3 and TFEB, two transcription factors and substrates of mTORC1. Thus, the lysosomal mTOR signaling complex represents a hub of cellular energy metabolism, and its dysregulation may lead to a number of human diseases. Here, we discuss the recent developments and highlight the open questions in this growing field.
    Journal of Cell Death 01/2015; 1(1). DOI:10.1515/cdth-2015-0001
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The target of rapamycin complex 1 (TORC1) is an evolutionarily conserved sensor of nutrient availability. Genetic and pharmacological studies in the yeast Saccharomyces cerevisiae have provided mechanistic insights on the regulation of TORC1 signaling in response to nutrients. Using a highly specific antibody that recognizes phosphorylation of the bona fide TORC1 target ribosomal protein S6 (Rps6) in yeast, we found that nutrients rapidly induce Rps6 phosphorylation in a TORC1-dependent manner. Moreover, we demonstrate that Ypk3, an AGC kinase which exhibits high homology to human S6 kinase (S6K), is required for the phosphorylation of Rps6 in vivo. Rps6 phosphorylation is completely abolished in cells lacking Ypk3 (ypk3Δ), whereas Sch9, previously reported to be the yeast ortholog of S6K, is dispensable for Rps6 phosphorylation. Phosphorylation-deficient mutations in regulatory motifs of Ypk3 abrogate Rps6 phosphorylation, and complementation of ypk3Δ cells with human S6 kinase restores Rps6 phosphorylation in a rapamycin-sensitive manner. Our findings demonstrate that Ypk3 is a critical component of the TORC1 pathway and that the use of a phospho-S6 specific antibody offers a valuable tool to identify new nutrient-dependent and rapamycin-sensitive targets in vivo.
    PLoS ONE 10(3):e0120250. DOI:10.1371/journal.pone.0120250 · 3.53 Impact Factor

Full-text (2 Sources)

Available from
May 28, 2014