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ER Stress Activates the TOR Pathway through Atf6

Dylan Allen1, Jin Seo1

  • 1Department of Biology, School of Arts and Sciences, Rogers State University, Claremore, OK, US.

Journal of Molecular Signaling
|September 14, 2018
PubMed

Insights

Endoplasmic reticulum (ER) stress activates the target of rapamycin (TOR) signaling pathway in Drosophila cells. This ER stress-induced TOR activation is mediated by the transcription factor activating transcription factor 6 (Atf6).

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cellular signaling pathways, including the target of rapamycin (TOR) and endoplasmic reticulum (ER) stress response, regulate vital cell functions.
  • Interconnections between these pathways are increasingly recognized, but detailed mechanisms of crosstalk remain largely undefined.

Purpose of the Study:

  • To investigate the crosstalk between the ER stress response and the TOR signaling pathway.
  • To elucidate the molecular mechanisms underlying ER stress-induced TOR activation.

Main Methods:

  • Utilized S2R+ Drosophila cells to study cellular signaling.
  • Employed ER stress-inducing drugs to trigger pathway activation.
  • Investigated the role of Activating Transcription Factor 6 (Atf6) and its processing enzymes (S1P/S2P) using knockdown experiments.

Main Results:

  • ER stress-inducing drugs were found to activate the TOR signaling pathway in Drosophila S2R+ cells.
  • Activating transcription factor 6 (Atf6) was identified as a key mediator responsible for ER stress-induced TOR activation.
  • Knockdown of site-1/2 proteases (S1P/S2P), essential for Atf6 processing, was necessary to link the ER stress and TOR pathways.

Conclusions:

  • Demonstrated a functional link between the ER stress response and TOR signaling in Drosophila.
  • Identified Atf6 as a crucial molecular link mediating the activation of TOR signaling by ER stress.
  • Highlighted the significance of Atf6 processing by S1P/S2P in connecting these two critical cellular pathways.
Keywords:
Atf6ER stressTOR pathway

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