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Chapter 25 : Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals

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Abstract:

A universal feature of all organisms is their ability to respond to nutrient availability by regulating growth and developmental programs. The identification of the target of rapamycin (TOR) pathway was a seminal discovery in the quest to understand the molecular mechanisms that govern such processes. TOR is an evolutionarily conserved serine/threonine kinase belonging to the family of phosphatidylinositol kinase-related kinases. Other members of this family include the mammalian DNA damage checkpoint kinases ATM and ATR,which are conserved from yeast to human, and DNA-PK and SMG1, which are not found in yeasts. TOR regulates growth (accumulation of mass), proliferation (accumulation in cell number), and survival in response to nutritional changes by diverse mechanisms that include regulation of anabolic and catabolic metabolism, nutrient uptake, protein translation and turnover, gene transcription, and the epigenome (reviewed in ).

Citation: Weisman R. 2017. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals, p 535-548. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0006-2016
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Figures

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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.

Citation: Weisman R. 2017. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals, p 535-548. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. 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.

Citation: Weisman R. 2017. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals, p 535-548. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0006-2016
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