The TOR signalling network from yeast to man

Abstract

The target of rapamycin, TOR, is an essential ser/thr protein kinase that functions in two distinct multiprotein complexes, TOR complex 1 and 2. The structure and functions of these complexes have been conserved from yeast to man. TOR complex 1 is inhibited by rapamycin and is thought to couple growth cues to cellular metabolism; TOR complex 2 is not inhibited by rapamycin and appears to regulate spatial aspects of growth such as cell polarity. Work done in a variety of model systems, continues to contribute to our current understanding of this TOR signalling network. Recent studies in flies and mammalian tissue culture cells have elucidated many signalling components upstream of TOR complex 1. These studies also suggest that aberrant mammalian TOR complex 1 signalling contributes to a number of pathologies ranging from metabolic diseases to hyperproliferative disorders and cancers. Consequently the efficacies of rapamycin and related compounds in treating such diseases are being evaluated in clinical trials.

Overproduction of non‐translatable mRNA silences. The transcription of Ty1 retrotransposons in S. cerevisiae via functional inactivation of the nuclear cap‐binding complex and subsequent hyperstimulation of the TORC1 pathway

“…TOR plays an essential role in progression through the G 1 phase of the eukaryotic cell cycle and growth (or entry into the G 0 quiescent phase) in response to a variety of environmental cues, such as nutrient availability and stress (De Virgilio and Loewith, 2006;Heitman et al, 1991;Martin and Hall, 2005). There are two structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast, encoded by TOR1 and TOR2, respectively (Helliwell et al, 1994).…”

“…Nitrogen and carbon are the two most important nutrients for yeast growth, and the TORC1 signalling pathway activates a cell-growth programme in response to nutrients such as nitrogen and carbon (De Virgilio and Loewith, 2006;Heitman et al, 1991;Martin and Hall, 2005). The TORC1 pathway plays a key role in nitrogen catabolite repression (NCR) -repression of nitrogen catabolic genes in the presence of good nitrogen source.…”

Construction of a rapamycin-susceptible strain of the unicellular red alga <i>Cyanidioschyzon merolae</i> for analysis of the target of rapamycin (TOR) function

“…We then successfully used the isolated strain as a host strain Construction of a rapamycin-susceptible strain of the unicellular red alga Cyanidioschyzon merolae for analysis of the target of rapamycin (TOR) function (Received December 3, 2016 The target of rapamycin (TOR) is a serine/threonine protein kinase that plays a central role in the regulation of cell growth and metabolism (Laplante and Sabatini, 2012). This protein, which is structurally and functionally conserved among eukaryotes (Virgilio and Loewith, 2006;Wullschleger et al, 2006), is found in two functionally distinct multi-protein complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TORC1 regulates cell growth and metabolism in response to nutrient and energy requirements (Virgilio and Loewith, 2006;Wullschleger et al, 2006) and its functions are specifically inhibited by rapamycin (Heitman et al, 1991).…”

“…This protein, which is structurally and functionally conserved among eukaryotes (Virgilio and Loewith, 2006;Wullschleger et al, 2006), is found in two functionally distinct multi-protein complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TORC1 regulates cell growth and metabolism in response to nutrient and energy requirements (Virgilio and Loewith, 2006;Wullschleger et al, 2006) and its functions are specifically inhibited by rapamycin (Heitman et al, 1991). TORC2, involved in the regulation of the cytoskeleton structure and spatial features of cell growth, is not inhibited by rapamycin (Virgilio and Loewith, 2006;Wullschleger et al, 2006).…”

“…TORC1 regulates cell growth and metabolism in response to nutrient and energy requirements (Virgilio and Loewith, 2006;Wullschleger et al, 2006) and its functions are specifically inhibited by rapamycin (Heitman et al, 1991). TORC2, involved in the regulation of the cytoskeleton structure and spatial features of cell growth, is not inhibited by rapamycin (Virgilio and Loewith, 2006;Wullschleger et al, 2006).…”