mTOR Is Essential for the Proteotoxic Stress Response, HSF1 Activation and Heat Shock Protein Synthesis

@article{Chou2012mTORIE,
  title={mTOR Is Essential for the Proteotoxic Stress Response, HSF1 Activation and Heat Shock Protein Synthesis},
  author={S. Chou and T. Prince and J. Gong and S. Calderwood},
  journal={PLoS ONE},
  year={2012},
  volume={7}
}
The target of rapamycin (TOR) is a high molecular weight protein kinase that regulates many processes in cells in response to mitogens and variations in nutrient availability. [...] Key Result HSF1 was phosphorylated on S326 immediately after heat shock and was triggered by other cell stressors including proteasome inhibitors and sodium arsenite.Expand
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Findings of PKA regulation of HSF1 through S320 phosphorylation add to the knowledge of the signaling networks converging on this factor and may contribute to elucidating its complex roles in the stress response and understanding HSF 1 dysregulation in disease. Expand
Phosphorylation of HSF1 by MAPK-Activated Protein Kinase 2 on Serine 121, Inhibits Transcriptional Activity and Promotes HSP90 Binding*
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A novel mechanism for the regulation of HSF1 by proinflammatory signaling is indicated and may permit HSF 1 to respond rapidly to extracellular events, permitting optimal physiological regulation. Expand
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HSP genes are regulated at the transcriptional level by heat shock transcription factor 1 (HSF1) that is activated by stress and binds to heat shock elements in HSP genes, and recent studies indicate important roles for histone modifications on H SP genes during heat shock. Expand
Heat shock factor 1 ameliorates proteotoxicity in cooperation with the transcription factor NFAT
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These results show the first mechanistic basis for the observation that HSF1 has a much more profound effect on proteostasis than individual Hsp or combination of different Hsps, and suggest a new pathway for ameliorating protein‐misfolding diseases. Expand
Protein Kinase A Regulates Molecular Chaperone Transcription and Protein Aggregation
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It is shown here that PKA is essential for effective transcription of HSP genes by HSF1, which triggers a cascade involvingHSF1 binding to the histone acetylase p300 and positive translation elongation factor 1 (p-TEFb) and phosphorylation of the c-terminal domain of RNA polymerase II, a key mechanism in the downstream steps of HSF 1-mediated transcription. Expand
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TLDR
Twelve Ser residues but no Thr or Tyr residues were identified that were phosphorylated in heat-activated HSF1, and no functional role could be ascribed to any of the other newly identified phosphoSer residues. Expand
Targeted Disruption of Heat Shock Transcription Factor 1 Abolishes Thermotolerance and Protection against Heat-inducible Apoptosis*
TLDR
It is concluded that 1) constitutive and inducibly expressed HSPs exhibit distinct physiological functions for cellular maintenance and adaptation, respectively, and 2) other mammalian HSFs or distinct evolutionarily conserved stress response pathways do not compensate for HSF1 in the physiological response to heat shock. Expand
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The heat shock protein response appears to be triggered primarily by nonnative proteins accumulating in a stressed cell and results in increased expression of heat shock proteins (HSPs), and HSPs and co-chaperone complexes regulate HSF1 activity at different levels. Expand
Transcriptional Activity of Heat Shock Factor 1 at 37 oC Is Repressed through Phosphorylation on Two Distinct Serine Residues by Glycogen Synthase Kinase 3α and Protein Kinases Cα and Cζ*
Heat shock factor 1 (HSF1) is the key transcriptional regulator of the heat shock genes that protect cells from environmental stress. However, because heat shock gene expression is deleterious toExpand
Transcriptional activity of heat shock factor 1 at 37 degrees C is repressed through phosphorylation on two distinct serine residues by glycogen synthase kinase 3 and protein kinases Calpha and Czeta.
TLDR
Regulation at 37 degrees C involves the action of three protein kinase cascades that repress HSF1 through phosphorylation of serine residues 303, 307, and 363 and may promote growth by suppressing the heat shock response. Expand
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