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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins

L Zhang1, J Chen, H Fu

  • 1Department of Pharmacology, Cell, and Developmental Biology, Emory University, Atlanta, GA 30322, USA.

Proceedings of the National Academy of Sciences of the United States of America
|July 21, 1999
PubMed

Insights

Apoptosis signal-regulating kinase 1 (ASK1) activity, which promotes cell death, is blocked by 14-3-3 proteins. This interaction, particularly at Ser-967, offers a survival pathway that suppresses apoptosis.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Apoptosis research

Background:

  • Apoptosis signal-regulating kinase 1 (ASK1) is crucial in cell death pathways triggered by various stimuli.
  • Stimuli include TNF-alpha, Fas, and chemotherapy drugs like cisplatin and paclitaxel.

Purpose of the Study:

  • To investigate the role of 14-3-3 proteins in regulating ASK1's proapoptotic activity.
  • To identify the specific interaction site between ASK1 and 14-3-3 proteins.

Main Methods:

  • Overexpression of 14-3-3 proteins in HeLa cells.
  • Disruption of the ASK1/14-3-3 protein interaction.
  • Analysis of ASK1-induced apoptosis.

Main Results:

  • Association with 14-3-3 proteins antagonizes ASK1's proapoptotic function.
  • ASK1 specifically binds 14-3-3 proteins at a site involving Ser-967.
  • Overexpression of 14-3-3 inhibited ASK1-induced apoptosis, while disruption accelerated cell death.

Conclusions:

  • 14-3-3 proteins act as negative regulators of ASK1.
  • A 14-3-3-mediated survival pathway targeting ASK1 may suppress apoptosis.
  • This interaction presents a novel mechanism for controlling programmed cell death.

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