Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2009, PMID: 19553685

Inactivation of mammalian target of rapamycin increases STAT1 nuclear content and transcriptional activity in alpha4- and protein phosphatase 2A-dependent fashion.

Fielhaber, Jill A; Han, Ying-Shan; Tan, Jason; Xing, Shuo; Biggs, Catherine M; Joung, Kwang-Bo; Kristof, Arnold S

Target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth, primarily via regulation of protein synthesis. In Saccharomyces cerevisiae, TOR can also suppress the transcription of stress response genes by a mechanism involving Tap42, a serine/threonine phosphatase subunit, and the transcription factor Msn2. A physical association between mammalian TOR (mTOR) and the transcription factor signal transducer and activator of transcription-1 (STAT1) was recently identified in human cells, suggesting a similar role for mTOR in the transcription of interferon-gamma-stimulated genes. In the current study, we identified a macromolecular protein complex composed of mTOR, STAT1, the Tap42 homologue alpha4, and the protein phosphatase 2A catalytic subunit (PP2Ac). Inactivation of mTOR enhanced its association with STAT1 and increased STAT1 nuclear content in PP2Ac-dependent fashion. Depletion of alpha4, PP2A, or mTOR enhanced the induction of early (i.e. IRF-1) and late (i.e. caspase-1, hiNOS, and Fas) STAT1-dependent genes. The regulation of IRF-1 or caspase-1 by mTOR was independent of other known mTOR effectors p70 S6 kinase and Akt. These results describe a new role for mTOR and alpha4/PP2A in the control of STAT1 nuclear content, and the expression of interferon-gamma-sensitive genes involved in immunity and apoptosis.

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Text Mining Data

caspase-1 — mTOR: " The regulation of IRF-1 or caspase-1 by mTOR was independent of other known mTOR effectors p70 S6 kinase and Akt "

IRF-1 — mTOR: " The regulation of IRF-1 or caspase-1 by mTOR was independent of other known mTOR effectors p70 S6 kinase and Akt "

Manually curated Databases

  • IRef Biogrid Interaction: PRKCD — STAT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PRKCD — STAT1 (colocalization, biochemical)
  • IRef Biogrid Interaction: STAT1 — MLST8 (colocalization, biochemical)
  • IRef Biogrid Interaction: IGBP1 — STAT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: IGBP1 — STAT1 (colocalization, biochemical)
  • IRef Biogrid Interaction: STAT1 — RPS6KB1 (colocalization, biochemical)
  • IRef Biogrid Interaction: STAT1 — PPP2R4 (colocalization, biochemical)
  • IRef Biogrid Interaction: STAT1 — PPP2R4 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: STAT1 — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: STAT1 — MTOR (colocalization, biochemical)
In total, 6 gene pairs are associated to this article in curated databases