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TOR modulates GCN4-dependent expression of genes turned on by nitrogen limitation
L Valenzuela1, C Aranda, A González
1Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico.
Abstract:
In Saccharomyces cerevisiae, the rapamycin-sensitive TOR signaling pathway plays an essential role in up-regulating translation initiation and cell cycle progression in response to nutrient availability. One of the mechanisms by which TOR regulates cell proliferation is by excluding the GLN3 transcriptional activator from the nucleus and, in consequence, preventing its transcriptional activation therein. We examined the possibility that the TOR cascade could also control the transcriptional activity of Gcn4p, which is known to respond to amino acid availability. The results presented in this paper indicate that GCN4 plays a role in the rapamycin-sensitive signaling pathway, regulating the expression of genes involved in the utilization of poor nitrogen sources, a previously unrecognized role for Gcn4p, and that the TOR pathway controls GCN4 activity by regulating the translation of GCN4 mRNA. This constitutes an additional TOR-dependent mechanism which modulates the action of transcriptional activators.
Insights
The target of rapamycin (TOR) pathway regulates cell growth by controlling Gcn4p translation. This reveals a new TOR-dependent mechanism for modulating transcriptional activators in response to nutrient availability.
Area of Science:
- Molecular biology
- Yeast genetics
- Cell signaling
Background:
- The rapamycin-sensitive TOR pathway is crucial for nutrient-dependent cell growth in Saccharomyces cerevisiae.
- TOR signaling regulates cell proliferation partly by controlling nuclear localization of the transcriptional activator Gln3p.
Purpose of the Study:
- To investigate whether the TOR cascade influences the transcriptional activity of Gcn4p, a known regulator of amino acid metabolism.
- To elucidate the role of Gcn4p in nutrient utilization and its regulation by the TOR pathway.
Main Methods:
- Investigated the interaction between the TOR pathway and Gcn4p activity.
- Analyzed the regulation of GCN4 mRNA translation by the TOR pathway.
- Examined the role of Gcn4p in the expression of genes involved in nitrogen source utilization.
Main Results:
- GCN4 plays a role in the rapamycin-sensitive signaling pathway.
- Gcn4p regulates genes involved in utilizing poor nitrogen sources, a novel function.
- The TOR pathway controls Gcn4p activity by regulating the translation of GCN4 mRNA.
Conclusions:
- The TOR pathway modulates Gcn4p activity through translational control of GCN4 mRNA.
- This represents an additional TOR-dependent mechanism for regulating transcriptional activators.
- Gcn4p has a previously unrecognized role in nitrogen metabolism regulation within the TOR signaling network.