Gene interactions and pathways from curated databases and text-mining
Genes Dev 2004, PMID: 15004009

mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability.

Mayer, Christine; Zhao, Jian; Yuan, Xuejun; Grummt, Ingrid

In cycling cells, transcription of ribosomal RNA genes by RNA polymerase I (Pol I) is tightly coordinated with cell growth. Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability. Inhibition of mTOR signaling by rapamycin inactivates TIF-IA and impairs transcription-initiation complex formation. Moreover, rapamycin treatment leads to translocation of TIF-IA into the cytoplasm. Rapamycin-mediated inactivation of TIF-IA is caused by hypophosphorylation of Se 44 (S44) and hyperphosphorylation of Se 199 (S199). Phosphorylation at these sites affects TIF-IA activity in opposite ways, for example, phosphorylation of S44 activates and S199 inactivates TIF-IA. The results identify a new target formTOR-signaling pathways and elucidate the molecular mechanism underlying mTOR-dependent regulation of RNA synthesis.

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Text Mining Data

TIF-IA → mTOR: " mTOR dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability "

Pol I → mammalian target of rapamycin (mTOR): " Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability "

mammalian target of rapamycin (mTOR) — TIF-IA: " Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA , a regulatory factor that senses nutrient and growth-factor availability "

Pol I — TIF-IA: " Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA , a regulatory factor that senses nutrient and growth-factor availability "

Manually curated Databases

  • IRef Biogrid Interaction: RRN3 — CDK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: PPP2R2A — RRN3 (direct interaction, pull down)
  • IRef Biogrid Interaction: CCNE1 — CDK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: CCNE1 — RRN3 (direct interaction, pull down)
  • IRef Hprd Interaction: RRN3 — POLR1B (in vitro)
  • IRef Hprd Interaction: RRN3 — POLR1B (in vivo)
  • IRef Hprd Interaction: EIF3L — RRN3 (in vivo)
  • IRef Hprd Interaction: EIF3L — RRN3 (in vitro)
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → CDK2/Cyclin E1 complex (CDK2-CCNE1) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → TIFIA (RRN3) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database mTOR signaling pathway: CDK2/Cyclin E1 complex (CDK2-CCNE1) → TIFIA (RRN3) (modification, activates)
    Evidence: mutant phenotype, assay
In total, 18 gene pairs are associated to this article in curated databases