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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

The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1

X Zou1, T Tsutsui, D Ray

  • 1Department of Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607, USA.

Molecular and Cellular Biology
|June 21, 2001
PubMed

Insights

CDC25A phosphatase interacts with apoptosis signal-regulating kinase 1 (ASK1), inhibiting its activity. This dual function promotes cell cycle progression and reduces oxidative stress sensitivity, contributing to cancer development.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • CDC25A phosphatase is known to promote cell cycle progression and is implicated as an oncogene.
  • Apoptosis signal-regulating kinase 1 (ASK1) is activated by cellular stresses and regulates MAPK and JNK/SAPK pathways.

Purpose of the Study:

  • To identify proteins interacting with CDC25A.
  • To elucidate the functional consequences of CDC25A and ASK1 interaction on cellular stress responses and cell cycle progression.

Main Methods:

  • Yeast two-hybrid screening to identify CDC25A-interacting proteins.
  • Coimmunoprecipitation and confocal microscopy to confirm protein association and localization.
  • Inducible transgene expression to study the effects of CDC25A on ASK1 signaling and cell death.

Main Results:

  • Apoptosis signal-regulating kinase 1 (ASK1) was identified as a CDC25A-interacting protein.
  • CDC25A physically associates with ASK1 in the cytoplasm and inhibits ASK1 kinase activity by reducing its homo-oligomerization.
  • Increased CDC25A expression suppressed oxidant-dependent activation of ASK1, p38, and JNK1, reducing sensitivity to oxidative stress-induced cell death.

Conclusions:

  • CDC25A possesses a dual function: promoting cell cycle progression and inhibiting stress-activated signaling pathways.
  • CDC25A's inhibition of ASK1 contributes to reduced cellular responsiveness to oxidative stress, potentially aiding oncogenic transformation.
  • The interaction between CDC25A and ASK1 provides a novel mechanism linking cell cycle control and stress response evasion in cancer.

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