Human Gene Set: BILANGES_RAPAMYCIN_SENSITIVE_VIA_TSC1_AND_TSC2

For the Mouse gene set with the same name, see BILANGES_RAPAMYCIN_SENSITIVE_VIA_TSC1_AND_TSC2

Standard name BILANGES_RAPAMYCIN_SENSITIVE_VIA_TSC1_AND_TSC2
Systematic name M2331
Brief description Genes translationally repressed by rapamycin (sirolimus) [PubChem=6610346] in MEF cells (embryonic fibroblast) lacking either TSC1 or TSC2 [GeneID=7248] [GeneID=7249] but not in the wild type cells.
Full description or abstract The tuberous sclerosis complex (TSC) proteins TSC1 and TSC2 regulate protein translation by inhibiting the serine/threonine kinase mTORC1 (for mammalian target of rapamycin complex 1). However, how TSC1 and TSC2 control overall protein synthesis and the translation of specific mRNAs in response to different mitogenic and nutritional stimuli is largely unknown. We show here that serum withdrawal inhibits mTORC1 signaling, causes disassembly of translation initiation complexes, and causes mRNA redistribution from polysomes to subpolysomes in wild-type mouse embryo fibroblasts (MEFs). In contrast, these responses are defective in Tsc1(-/-) or Tsc2(-/-) MEFs. Microarray analysis of polysome- and subpolysome-associated mRNAs uncovered specific mRNAs that are translationally regulated by serum, 90% of which are TSC1 and TSC2 dependent. Surprisingly, the mTORC1 inhibitor, rapamycin, abolished mTORC1 activity but only affected approximately 40% of the serum-regulated mRNAs. Serum-dependent signaling through mTORC1 and polysome redistribution of global and individual mRNAs were restored upon re-expression of TSC1 and TSC2. Serum-responsive mRNAs that are sensitive to inhibition by rapamycin are highly enriched for terminal oligopyrimidine and for very short 5' and 3' untranslated regions. These data demonstrate that the TSC1/TSC2 complex regulates protein translation through mainly mTORC1-dependent mechanisms and implicates a discrete profile of deregulated mRNA translation in tuberous sclerosis pathology.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17562867   Authors: Bilanges B,Argonza-Barrett R,Kolesnichenko M,Skinner C,Nair M,Chen M,Stokoe D
Exact source Table 4S
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Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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