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Updated: Jun 11, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Regulation of apoptosis signal-regulating kinase 1 in redox signaling

Kazumi Katagiri1, Atsushi Matsuzawa, Hidenori Ichijo

  • 1Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.

Methods in Enzymology
|July 9, 2010
PubMed

Insights

Thioredoxin (Trx) regulates Apoptosis signal-regulating kinase 1 (ASK1) activity by binding to it under normal conditions. Oxidative stress causes Trx to change conformation, releasing ASK1 and activating its signaling pathways.

Area of Science:

  • Cellular signaling
  • Oxidative stress response
  • Protein-protein interactions

Background:

  • Apoptosis signal-regulating kinase 1 (ASK1) is a key kinase in stress response pathways.
  • ASK1 activation by oxidative stress is not fully understood.
  • Thioredoxin (Trx) is an antioxidant protein that inhibits ASK1 activity under normal conditions.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of ASK1 by Trx.
  • To understand the role of redox conditions in ASK1-Trx interaction.
  • To provide methods for studying intracellular redox signaling.

Main Methods:

  • Review of regulatory mechanisms of ASK1 by Trx.
  • Description of in vitro binding assays for Trx and ASK1 under varying redox conditions.
  • Presentation of Western blot and in vitro kinase assays for detecting ASK1 activation in cells.

Main Results:

  • Trx directly binds and inhibits ASK1 under normal conditions.
  • Oxidative stress induces conformational changes in Trx, leading to dissociation from ASK1 and full activation.
  • Methods for monitoring Trx-ASK1 interaction and ASK1 activation were established.

Conclusions:

  • The interaction between Trx and ASK1 is redox-dependent.
  • Understanding Trx regulation of ASK1 is crucial for deciphering intracellular redox signaling.
  • The presented techniques facilitate research into redox signaling pathways.

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