Gene Set: PENG_RAPAMYCIN_RESPONSE_DN

Standard name PENG_RAPAMYCIN_RESPONSE_DN
Systematic name M18854
Brief description Genes down-regulated in BJUB cells (B-lymphoma) in response to rapamycin (sirolimus) [PubChem=6610346] treatment.
Full description or abstract RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcriptional profiling, we show that, in human BJAB B-lymphoma cells and murine CTLL-2 T lymphocytes, rapamycin treatment affects the expression of many genes involved in nutrient and protein metabolism. The rapamycin-induced transcriptional profile is distinct from those induced by glucose, glutamine, or leucine deprivation but is most similar to that induced by amino acid deprivation. In particular, rapamycin treatment and amino acid deprivation up-regulate genes involved in nutrient catabolism and energy production and down-regulate genes participating in lipid and nucleotide synthesis and in protein synthesis, turnover, and folding. Surprisingly, however, rapamycin had effects opposite from those of amino acid starvation on the expression of a large group of genes involved in the synthesis, transport, and use of amino acids. Supported by measurements of nutrient use, the data suggest that RAFT1 is an energy and nutrient sensor and that rapamycin mimics a signal generated by the starvation of amino acids but that the signal is unlikely to be the absence of amino acids themselves. These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 12101249   Authors: Peng T,Golub TR,Sabatini DM
Exact source Suppl. data for Fig. 1: sheet2_rapamycin dw
Related gene sets (show 9 additional gene sets from the source publication)

(show 259 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Pablo Tamayo (Broad Institute)
Source platform UnigeneIdentifiers
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: Renamed from PENG_RAPAMYCIN_DN

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