Fission Yeast TORC1 Promotes Cell Proliferation through Sfp1, a Transcription Factor Involved in Ribosome Biogenesis
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ABSTRACT:
ORGANISM(S): Schizosaccharomyces pombe
PROVIDER: GSE201580 | GEO | 2023/04/01
REPOSITORIES: GEO
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Project description:Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 signaling pathway inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprogramming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Although rapamycin showed a much more subtle effect on global translation than did caffeine, rapamycin was more effective in prolonging chronological lifespan. Rapamycin prolonged the lifespan of non-growing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond.
2013-05-05 | E-MTAB-1489 | biostudies-arrayexpress
Project description:Snf1 and TORC1 are two global regulators that sense the nutrient availability and regulate the cell growth in yeast Saccharomyces cerevisiae. Here we undertook a systems biology approach to study the effect of deletion of these genes and investigate the interaction between Snf1 and TORC1 in regulation of gene expression and cell metabolism.
2011-10-20 | GSE24421 | GEO
Project description:A PP2A-Pab1-mediated crosstalk between TORC1 & TORC2 regulates the differentiation response in fission yeast
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Project description:Snf1 and TORC1 are two global regulators that sense the nutrient availability and regulate the cell growth in yeast Saccharomyces cerevisiae. Here we undertook a systems biology approach to study the effect of deletion of these genes and investigate the interaction between Snf1 and TORC1 in regulation of gene expression and cell metabolism. 3 mutant strains (snf1?, tor1?, snf1?tor1?) together with 1 reference strain grown under both glucose-limited or amonia-limited defined media with three biological replicates for each strain
2011-10-19 | E-GEOD-24421 | biostudies-arrayexpress
Project description:Reduced ribosome biogenesis in response to environmental conditions is a key feature of cell adaptation to stress. For example, ribosomal genes are transcriptionally repressed when cells are exposed to tunicamycin, a protein glycosylation inhibitor that induces endoplasmic reticulum stress and blocks vesicular trafficking in the secretory pathway. Here, we describe a novel regulatory model, in which tunicamycin-mediated stress induces the accumulation of long-chain sphingoid bases and subsequent activation of Pkh1/2 signaling, which leads to decreased expression of ribosomal protein genes via the downstream effectors Pkc1 and Sch9. Target of rapamycin complex 1 (TORC1), an upstream activator of Sch9, is also required. This pathway links ribosome biogenesis to alterations in membrane lipid composition under tunicamycin-induced stress conditions. Our results suggest that sphingolipid/Pkh1/2-TORC1/Sch9 signaling is an important determinant for adaptation to tunicamycin-induced stress.
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Project description:Purpose:To identify the targets of TORC1 during spore germination in budding yeast Results:We obtained the transcriptomes of germinating spores in the presence and absence of rapamycin with and average Read Count = 14,009,863 and an Average Overall alignment: 95.23%. Differentialy expressed genes were identified by comparing the spore germination at various time points in the presence and absence of Rapamycin. Conclusions: Our transcriptomic analyses has revealed a role for TORC1 in regulating the glucose response genes
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Project description:To determine how TORC1 and PKA cooperate to regulate cell growth, we performed temporal analysis of gene expression in yeast switched from a non-fermentable substrate, to glucose, in the presence and absence of TORC1 and PKA inhibitors. Quantitative analysis of these data reveals that PKA drives the expression of key cell growth genes during transitions into, and out of, the rapid growth state in glucose, while TORC1 is important for the steady-state expression of the same genes.
2019-07-19 | GSE133591 | GEO
Project description:The Target Of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intra- and extracellular cues. Here we report the first bona fide substrate of yeast TORC1: the AGC-kinase Sch9. Six amino acids in the c-terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin-treatment as well as carbon- or nitrogen-starvation and transiently reduced following application of osmotic, oxidative or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1-independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt. Keywords: time course, cell type.
2007-04-28 | GSE7660 | GEO
Project description:Target of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells preserve a small pool of dormant ribosomes under nutrient-limited conditions. The regulation of dormant ribosomes is poorly characterized. Here, we show that upon inhibition of TORC1 by rapamycin or nitrogen starvation, Stm1 (suppressor of target of Myb protein 1) forms non-translating, dormant 80S ribosomes. Furthermore, Stm1-bound 80S ribosomes are protected from proteasomal degradation. Upon re-feeding, TORC1 directly phosphorylates and inhibits Stm1, thereby reactivating translation. Finally, SERBP1 (SERPINE1 mRNA binding protein), a mammalian ortholog of Stm1, forms dormant 80S ribosomes upon mTORC1 inhibition in mammalian cells. Thus, TORC1 regulates ribosomal dormancy in an evolutionarily conserved manner via a ribosome preservation factor.
2023-01-19 | PXD037117 | Pride
Project description:The Target Of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intra- and extracellular cues. Here we report the first bona fide substrate of yeast TORC1: the AGC-kinase Sch9. Six amino acids in the c-terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin-treatment as well as carbon- or nitrogen-starvation and transiently reduced following application of osmotic, oxidative or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1-independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt. Keywords: time course, cell type. Global transcriptional analysis of rapamycin response was conducted on cells expressing either a wild-type, Sch9(WT), or TOR-independent allele of Sch9, Sch9(2D3E). Reference samples used were cells collected immediately prior to rapamycin treatment for the respective cell genotypes. Test samples were collected 20, 30, 60, 90, 120, and 180min post rapamycin treatment.
2010-09-15 | E-GEOD-7660 | biostudies-arrayexpress