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Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals

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  • Author: Ronit Weisman1
  • Editor: Joseph Heitman2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Natural and Life Sciences, The Open University of Israel, Raanana, 435379, Israel; 2: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710
  • Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.FUNK-0006-2016
  • Received 27 March 2016 Accepted 11 July 2016 Published 21 October 2016
  • Ronit Weisman, ronitwe@openu.ac.il
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  • Abstract:

    All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

  • Citation: Weisman R. 2016. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals. Microbiol Spectrum 4(5):FUNK-0006-2016. doi:10.1128/microbiolspec.FUNK-0006-2016.

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/content/journal/microbiolspec/10.1128/microbiolspec.FUNK-0006-2016
2016-10-21
2017-04-28

Abstract:

All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

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Image of FIGURE 1
FIGURE 1

TORC1 and TORC2 subunits and downstream AGC kinases in mammalian, , and cells. TORC1 and TORC2 have shared and unique components. The human protein Raptor is TORC1-specific and is conserved in both yeast species. The human proteins Rictor and Sin1 are TORC2-specific subunits and are conserved in both yeast species. The target kinases of TORC1 and TORC2 are shown as green parallelograms.

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.FUNK-0006-2016
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Image of FIGURE 2
FIGURE 2

TORC1 is activated by GTPases to promote growth and inhibit starvation responses. TORC1 (TORC1) and TORC1 (TORC1) are activated by the GTPase complex Gtr1/Gtr2. The complex is active when Gtr1 is bound to GTP and Gtr2 is bound to GDP. Vam6 is a guanine exchange factor (GEF) for Gtr1 that is conserved between and . In , the Gtr1/Gtr2 complex is associated with the EGO complex and is controlled by the SEACIT (which acts as GTPase activating protein, GAP), SEACAT, and Lst4-Lst7 complexes. These complexes have as yet unidentified equivalents in . TORC1 is also regulated by the Rhb1 GTPase (Rheb in mammals) and the TSC (tuberous sclerosis complex, a tumor suppressor complex in mammals), which acts as a GAP towards Rhb1.

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.FUNK-0006-2016
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