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Transcriptional profiling of Rapamycin treatment in yeast cells lacking the Ptc1 protein phosphatase.


ABSTRACT: We are interested in the study of the already reported sensitivity of yeast cells lacking the type 1 protein phosphatase Ptc1 to the drug rapamycin. In order to carry out our studies, we analyzed the changes in the transcription profile that a short-term incubation with rapamycin (200 ng/mL) has in both, wild type and ptc1 cells. It has been shown that inhibition of the TOR pathway by treatment with rapamycin has profound effects on the global transcriptional profile. We confirmed the previously described transcription changes induced by the drug in wild type cells. Under our working conditions rapamycin increased, in wild type cells, at least 2-fold the expression of 667 genes, whereas it decreased the mRNA level of 721 genes (13.8% and 14.9% of genes with measurable expression level, respectively). Gene ontology analysis shows that, as previously documented, many induced genes falls into the NCR, Msn2/Msn4 regulated stress response or Retrograde response categories, whereas genes encoding cytoplasmic, but not mitochondrial, ribosomal proteins and the so called RIBI regulon where largely repressed. Deletion of PTC1 decreases the number of genes induced or repressed at least 2-fold by rapamycin treatment. Remarkably, lack of Ptc1 seems to lead to a general attenuation of changes triggered by rapamycin. The wt and the ptc1 mutant strains were analyzed in this series. We compared the expression profile of each strain treated with Rapamycin (200 ng/ml for 1h) with that of the same strain mock-treated (90% ethanol, 10% Tween-20). A Dye-swap was carried out for each RNA sample. Total number of chips analyzed: 4

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Antonio Casamayor 

PROVIDER: E-GEOD-11530 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Normal function of the yeast TOR pathway requires the type 2C protein phosphatase Ptc1.

González Asier A   Ruiz Amparo A   Casamayor Antonio A   Ariño Joaquín J  

Molecular and cellular biology 20090309 10


Yeast ptc1 mutants are rapamycin and caffeine sensitive, suggesting a functional connection between Ptc1 and the TOR pathway that is not shared by most members of the type 2C phosphatase family. Genome-wide profiling revealed that the ptc1 mutation largely attenuates the transcriptional response to rapamycin. The lack of Ptc1 significantly prevents the nuclear translocation of Gln3 and Msn2 transcription factors to the nucleus, as well as the dephosphorylation of the Npr1 kinase, in response to  ...[more]

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