Abstract
The target of rapamycin (TOR) signaling pathway allows eukaryotic cells to regulate their growth in response to nutritional cues [1, 2]. In S. cerevisiae, TOR controls the expression of genes involved in several nutrient-responsive biosynthetic pathways [3-7]. In particular, we have demonstrated that TOR negatively regulates a concise cluster of genes (termed RTG target genes) that encode mitochondrial and peroxisomal enzymes required for de novo amino acid biosynthesis [7]. TOR acts in part by regulating the subcellular localization of the Rtg1/Rtg3 transcription factor complex. Nuclear entry of this complex requires the cytoplasmic protein Rtg2, whose precise function has remained ill defined. Here we establish that the likely role of Rtg2 is to antagonize the activity of another protein, Mks1, which we demonstrate is itself a negative regulator of RTG target gene activation. Results of epistasis analyses suggest that Rtg2 and Mks1 act downstream of TOR and upstream of Rtg1 and Rtg3. Moreover, we find that Mks1 phosphorylation responds to TOR as well as to each of the Rtg1-Rtg3 proteins, indicative of complex regulation within this branch of TOR signaling. In addition to RTG target genes, microarray analysis reveals robust expression of lysine biosynthetic genes in mks1Δ cells, which depends on a functional RTG pathway. This latter result provides a molecular explanation for the previous identification of MKS1 as LYS80, a negative regulator of lysine biosynthesis [8].
| Original language | English (US) |
|---|---|
| Pages (from-to) | 389-395 |
| Number of pages | 7 |
| Journal | Current Biology |
| Volume | 12 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 5 2002 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
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Mks1 in concert with TOR signaling negatively regulates RTG target gene expression in S. cerevisiae. / Dilova, Ivanka; Chen, Ching Yi; Powers, Ted.
In: Current Biology, Vol. 12, No. 5, 05.03.2002, p. 389-395.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mks1 in concert with TOR signaling negatively regulates RTG target gene expression in S. cerevisiae
AU - Dilova, Ivanka
AU - Chen, Ching Yi
AU - Powers, Ted
PY - 2002/3/5
Y1 - 2002/3/5
N2 - The target of rapamycin (TOR) signaling pathway allows eukaryotic cells to regulate their growth in response to nutritional cues [1, 2]. In S. cerevisiae, TOR controls the expression of genes involved in several nutrient-responsive biosynthetic pathways [3-7]. In particular, we have demonstrated that TOR negatively regulates a concise cluster of genes (termed RTG target genes) that encode mitochondrial and peroxisomal enzymes required for de novo amino acid biosynthesis [7]. TOR acts in part by regulating the subcellular localization of the Rtg1/Rtg3 transcription factor complex. Nuclear entry of this complex requires the cytoplasmic protein Rtg2, whose precise function has remained ill defined. Here we establish that the likely role of Rtg2 is to antagonize the activity of another protein, Mks1, which we demonstrate is itself a negative regulator of RTG target gene activation. Results of epistasis analyses suggest that Rtg2 and Mks1 act downstream of TOR and upstream of Rtg1 and Rtg3. Moreover, we find that Mks1 phosphorylation responds to TOR as well as to each of the Rtg1-Rtg3 proteins, indicative of complex regulation within this branch of TOR signaling. In addition to RTG target genes, microarray analysis reveals robust expression of lysine biosynthetic genes in mks1Δ cells, which depends on a functional RTG pathway. This latter result provides a molecular explanation for the previous identification of MKS1 as LYS80, a negative regulator of lysine biosynthesis [8].
AB - The target of rapamycin (TOR) signaling pathway allows eukaryotic cells to regulate their growth in response to nutritional cues [1, 2]. In S. cerevisiae, TOR controls the expression of genes involved in several nutrient-responsive biosynthetic pathways [3-7]. In particular, we have demonstrated that TOR negatively regulates a concise cluster of genes (termed RTG target genes) that encode mitochondrial and peroxisomal enzymes required for de novo amino acid biosynthesis [7]. TOR acts in part by regulating the subcellular localization of the Rtg1/Rtg3 transcription factor complex. Nuclear entry of this complex requires the cytoplasmic protein Rtg2, whose precise function has remained ill defined. Here we establish that the likely role of Rtg2 is to antagonize the activity of another protein, Mks1, which we demonstrate is itself a negative regulator of RTG target gene activation. Results of epistasis analyses suggest that Rtg2 and Mks1 act downstream of TOR and upstream of Rtg1 and Rtg3. Moreover, we find that Mks1 phosphorylation responds to TOR as well as to each of the Rtg1-Rtg3 proteins, indicative of complex regulation within this branch of TOR signaling. In addition to RTG target genes, microarray analysis reveals robust expression of lysine biosynthetic genes in mks1Δ cells, which depends on a functional RTG pathway. This latter result provides a molecular explanation for the previous identification of MKS1 as LYS80, a negative regulator of lysine biosynthesis [8].
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UR - http://www.scopus.com/inward/citedby.url?scp=0037022532&partnerID=8YFLogxK
U2 - 10.1016/S0960-9822(02)00677-2
DO - 10.1016/S0960-9822(02)00677-2
M3 - Article
C2 - 11882290
AN - SCOPUS:0037022532
VL - 12
SP - 389
EP - 395
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 5
ER -