Abstract
The heterodimeric bZip/HLH transcription factors Rtg1p and Rtg3p regulate the expression of a concise set of metabolic genes (termed RTG target genes) required for de novo biosynthesis of glutamate and glutamine. Several components have now been identified that control both the intracellular localization as well as activity of the Rtg1p·Rtg3p complex, yet the precise upstream regulatory signals involved remain unclear. For example, it has been proposed that Btg1p·Rtg3p activity is repressed by glutamate, acting through the mitochondrial retrograde response pathway or, alternatively, by glutamine, acting through the Tor kinase pathway. Here we demonstrate that RTG target gene regulation is remarkably complex, with glutamate and glutamine as well as ammonia collaborating as potentially distinct signals to regulate RTG target gene expression. We show that both Tor and these nutrient-based signals converge on Mks1p, the immediate upstream inhibitor of Rtg1p·Rtg3p, and that a direct correlation exists between the degree of Mks1p phosphorylation and the extent of RTG target gene repression. Finally, we find that Tor- and glutamine-mediated RTG-target gene repression can be experimentally uncoupled, indicating that glutamine and Tor act, at least in part, independently to inhibit this pathway.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 46527-46535 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 279 |
| Issue number | 45 |
| DOIs | |
| State | Published - Nov 5 2004 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1p·Rtg3p-dependent target genes. / Dilova, Ivanka; Aronova, Sofia; Chen, Jenny C Y; Powers, Ted.
In: Journal of Biological Chemistry, Vol. 279, No. 45, 05.11.2004, p. 46527-46535.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1p·Rtg3p-dependent target genes
AU - Dilova, Ivanka
AU - Aronova, Sofia
AU - Chen, Jenny C Y
AU - Powers, Ted
PY - 2004/11/5
Y1 - 2004/11/5
N2 - The heterodimeric bZip/HLH transcription factors Rtg1p and Rtg3p regulate the expression of a concise set of metabolic genes (termed RTG target genes) required for de novo biosynthesis of glutamate and glutamine. Several components have now been identified that control both the intracellular localization as well as activity of the Rtg1p·Rtg3p complex, yet the precise upstream regulatory signals involved remain unclear. For example, it has been proposed that Btg1p·Rtg3p activity is repressed by glutamate, acting through the mitochondrial retrograde response pathway or, alternatively, by glutamine, acting through the Tor kinase pathway. Here we demonstrate that RTG target gene regulation is remarkably complex, with glutamate and glutamine as well as ammonia collaborating as potentially distinct signals to regulate RTG target gene expression. We show that both Tor and these nutrient-based signals converge on Mks1p, the immediate upstream inhibitor of Rtg1p·Rtg3p, and that a direct correlation exists between the degree of Mks1p phosphorylation and the extent of RTG target gene repression. Finally, we find that Tor- and glutamine-mediated RTG-target gene repression can be experimentally uncoupled, indicating that glutamine and Tor act, at least in part, independently to inhibit this pathway.
AB - The heterodimeric bZip/HLH transcription factors Rtg1p and Rtg3p regulate the expression of a concise set of metabolic genes (termed RTG target genes) required for de novo biosynthesis of glutamate and glutamine. Several components have now been identified that control both the intracellular localization as well as activity of the Rtg1p·Rtg3p complex, yet the precise upstream regulatory signals involved remain unclear. For example, it has been proposed that Btg1p·Rtg3p activity is repressed by glutamate, acting through the mitochondrial retrograde response pathway or, alternatively, by glutamine, acting through the Tor kinase pathway. Here we demonstrate that RTG target gene regulation is remarkably complex, with glutamate and glutamine as well as ammonia collaborating as potentially distinct signals to regulate RTG target gene expression. We show that both Tor and these nutrient-based signals converge on Mks1p, the immediate upstream inhibitor of Rtg1p·Rtg3p, and that a direct correlation exists between the degree of Mks1p phosphorylation and the extent of RTG target gene repression. Finally, we find that Tor- and glutamine-mediated RTG-target gene repression can be experimentally uncoupled, indicating that glutamine and Tor act, at least in part, independently to inhibit this pathway.
UR - http://www.scopus.com/inward/record.url?scp=8744281675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8744281675&partnerID=8YFLogxK
U2 - 10.1074/jbc.M409012200
DO - 10.1074/jbc.M409012200
M3 - Article
C2 - 15326168
AN - SCOPUS:8744281675
VL - 279
SP - 46527
EP - 46535
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 45
ER -