Human Gene Set: RAPA_EARLY_UP.V1_DN


Standard name RAPA_EARLY_UP.V1_DN
Systematic name M2643
Brief description Genes down-regulated in BJAB (lymphoma) cells by rapamycin (sirolimus) [PubChem=6610346].
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 C6: Oncogenic Signature
Source publication Pubmed 12101249   Authors: Peng T,Golub TR,Sabatini DM
Exact source Rapa60 and Rapa120 vs ET60 and ET120; top 200 genes (diff. of means)
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Source species Homo sapiens
Contributed by Pablo Tamayo (Broad Institute)
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identifier namespace		 HUMAN_GENE_SYMBOL
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