Target of rapamycin (TOR) regulates cellular homeostasis by coordinating cellular growth pathways in response to different environmental signals. Rapamycin, an allosteric TOR complex 1 (TORC1) inhibitor, has proven to be invaluable for elucidating various aspects of the TOR signalling pathway; however, its applications are limited due to its inability to completely suppress TORC2. In the present study, we examined the effects of a newly discovered potent TOR inhibitor, Torin2, which inhibits both TORC1 and TORC2, on Saccharomyces cerevisiae growth. Genome-scale expression profiling of Torin2 treated yeast cells showed an expression profile similar to that of other TOR inhibitors such as rapamycin and caffeine. Distinct inhibition of cell growth by Torin2 treatment is indicated by the fact that a smaller number of transcripts are altered, compared to the changes after rapamycin and caffeine treatments. Our results revealed that Torin2 leads to increased expression of the calcineurin pathway genes favouring a synergistic therapeutic response of Torin2 in combination with calcineurin inhibitors. Further, Torin2 causes defective bud site selection during asymmetric cell division, indicating a role of TOR signalling in regulation of the budding pattern. Torin2 treated yeast cells exhibit increased expression of metalloreductases which affects iron homeostasis leading to iron toxicity. Notably, the enhanced expression of TOR1 and TOR2 rescue the Torin2 augmented iron toxicity of yeast cell. This study has revealed novel conduits and our results suggest that using Torin2 will enable the dissection of TORC2 mediated functions of the TOR signalling pathway.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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