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Updated: Aug 25, 2026

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

Interaction of apoptosis signal-regulating kinase 1 with isoforms of 14-3-3 proteins

Romesh R Subramanian1, Hongying Zhang, Haining Wang

  • 1Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Experimental Cell Research
|March 17, 2004
PubMed

Insights

14-3-3 proteins bind to Apoptosis signal-regulating kinase 1 (ASK1), inhibiting its pro-apoptotic function. This interaction alters ASK1

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis signal-regulating kinase 1 (ASK1) mediates cell death pathways.
  • ASK1 activity is regulated by protein interactions, including with 14-3-3zeta.
  • The 14-3-3 protein family is known to regulate various cellular processes.

Purpose of the Study:

  • To investigate the interaction between ASK1 and various 14-3-3 isoforms.
  • To determine the functional consequences of ASK1/14-3-3 binding on ASK1 activity and localization.
  • To elucidate the mechanism by which 14-3-3 proteins regulate ASK1-induced apoptosis.

Main Methods:

  • Co-immunoprecipitation assays to confirm ASK1/14-3-3 binding.
  • Mutational analysis of ASK1 and 14-3-3 interaction sites.
  • Confocal microscopy to track intracellular localization of ASK1.
  • Apoptosis assays to assess the functional impact of 14-3-3 expression.

Main Results:

  • ASK1 binds to multiple 14-3-3 isoforms, indicating a general interaction property.
  • The ASK1/14-3-3 interaction is mediated by the 14-3-3 amphipathic groove.
  • 14-3-3 expression suppresses ASK1-induced apoptosis and causes ASK1 translocation to a perinuclear (likely ER) localization.
  • A mutant ASK1 defective in 14-3-3 binding (ASK1(S967A)) did not show altered subcellular distribution.

Conclusions:

  • 14-3-3 proteins broadly interact with ASK1.
  • 14-3-3 proteins inhibit ASK1's pro-apoptotic function.
  • Regulation of ASK1 subcellular localization is a key mechanism by which 14-3-3 proteins control ASK1 activity.

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