Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2002-7-8
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10085239, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10390815, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10464095, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10582122, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10611304, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10617575, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10737792, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10783168, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10856289, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-10888876, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11069888, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11106749, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11137008, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11238775, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11344107, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11358866, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11426655, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11504907, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11504908, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11691993, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-11729323, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-1348927, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-1975037, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-3896338, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-3909197, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-6342356, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-6882397, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-7518356, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-7822316, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-7929610, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-8008069, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-8429048, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-8672289, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-8741837, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-8761456, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-8778023, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-9242918, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-9356453, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-9421459, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-9600904, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-9603962, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-9619450, http://linkedlifedata.com/resource/pubmed/commentcorrection/12101249-9843981
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5575-84
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12101249-Humans, pubmed-meshheading:12101249-Animals, pubmed-meshheading:12101249-Mice, pubmed-meshheading:12101249-Amino Acids, pubmed-meshheading:12101249-Glucose, pubmed-meshheading:12101249-Starvation, pubmed-meshheading:12101249-Immunosuppressive Agents, pubmed-meshheading:12101249-Cell Line, pubmed-meshheading:12101249-Carrier Proteins, pubmed-meshheading:12101249-T-Lymphocytes, pubmed-meshheading:12101249-B-Lymphocytes, pubmed-meshheading:12101249-Signal Transduction, pubmed-meshheading:12101249-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:12101249-Down-Regulation, pubmed-meshheading:12101249-Gene Expression, pubmed-meshheading:12101249-Gene Expression Profiling, pubmed-meshheading:12101249-Lymphoma, B-Cell, pubmed-meshheading:12101249-Up-Regulation, pubmed-meshheading:12101249-Sirolimus, pubmed-meshheading:12101249-Ribosomal Protein S6 Kinases
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