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| Status |
Public on Feb 05, 2014 |
| Title |
Isp7 is a novel regulator of amino acid uptake in the TOR signaling pathway |
| Platform organisms |
Schizosaccharomyces pombe; Saccharomyces cerevisiae |
| Sample organism |
Schizosaccharomyces pombe |
| Experiment type |
Expression profiling by array
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| Summary |
We show that the sensitivity of tsc mutant cells to rapamycin is mediated by TORC1 and can be suppressed by overexpression of the 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling. suppressed by overexpression of the putative 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel master regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling.
TOR proteins reside in two distinct complexes, TOR complex 1 and 2 (TORC1 and TORC2) that are central for the regulation of cellular growth, proliferation and survival. TOR is also the target for the immunosuppressive and anti-cancer drug rapamycin. In Schizosaccharaomyces pombe, disruption of the TSC complex, mutations in which can lead to the Tuberous Sclerosis syndrome in humans, results in a rapamycin sensitive phenotype under poor nitrogen conditions. We show here that the sensitivity to rapamycin is mediated via inhibition of TORC1 and suppressed by overexpression of isp7+, a member of the family of 2-oxoglutarate-Fe(II) dependent oxygenases. The transcript level of isp7+ is negatively regulated by TORC1 but positively regulated by TORC2. Yet, we find extensive similarity between the transcriptome of cells disrupted for isp7+ and cells mutated in the catalytic subunit of TORC1. Moreover, Isp7 regulates amino acid permease expression similarly to TORC1 and in contrast to TORC2. Overexpression of isp7+ induces TORC1-dependent phosphorylation of ribosomal protein Rps6, while inhibiting TORC2-dependent phosphorylation and activation of the AGC-like kinase Gad8. Taken together, our findings suggest a central role for Isp7 in amino acid homeostasis and the presence of isp7+-dependent regulatory loops that affect both TORC1 and TORC2.
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| Overall design |
6 Samples (arrays) were performed. We generated pairwise comparison between DISP7 and WT, using Partek Genomics Suite. Genes with p≤5%[FDR] and a fold-change difference of ≥2\1.5 or <-2\-1.5 were selected.
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| Contributor(s) |
Laor D, Cohen A, Pasmanik-Chor M, Oron-Karni V, Kupiec M, Weisman R |
| Citation(s) |
24344203 |
| Submission date |
Nov 26, 2013 |
| Last update date |
Feb 21, 2017 |
| Contact name |
Metsada Pasmanik-Chor |
| E-mail(s) |
metsada@tauex.tau.ac.il
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| Organization name |
Tel Aviv University
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| Department |
Biology
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| Lab |
Bioinformatics Unit
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| Street address |
Ramat Aviv
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| City |
Tel Aviv |
| ZIP/Postal code |
69978 |
| Country |
Israel |
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| Platforms (1) |
| GPL2529 |
[Yeast_2] Affymetrix Yeast Genome 2.0 Array |
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| Samples (6)
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| GSM1275656 |
S. pombe wild type cells, control - replicate 1 |
| GSM1275657 |
S. pombe wild type cells, control - replicate 2 |
| GSM1275658 |
S. pombe wild type cells, control - replicate 3 |
| GSM1275659 |
S. pombe cells, lacking isp7+ - replicate 1 |
| GSM1275660 |
S. pombe cells, lacking isp7+ - replicate 2 |
| GSM1275661 |
S. pombe cells, lacking isp7+ - replicate 3 |
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| Relations |
| BioProject |
PRJNA229977 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE52759_RAW.tar |
6.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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