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

Published on: December 27, 2016

Mammalian sterile 20-like kinase 3 (MST3) mediates oxidative-stress-induced cell death by modulating JNK activation

Ce-Belle Chen1, Jowin K W Ng, Poh-Heok Choo

  • 1Division of Cancer and Developmental Cell Biology, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore. ce-belle.chen@green.oxon.org

Bioscience Reports
|July 17, 2009
PubMed

Insights

Mammalian sterile 20-like kinase 3 (MST3) deficiency confers resistance to hydrogen peroxide (H2O2) by suppressing the JNK survival pathway and upregulating heme oxygenase-1 (HO-1). This reveals MST3

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • MST3 (mammalian sterile 20-like kinase 3) is implicated in cell death pathways.
  • The precise mechanisms of MST3's role in cell death, particularly in response to oxidative stress, remain unclear.

Purpose of the Study:

  • To elucidate the role of MST3 in hydrogen peroxide (H2O2)-induced cell death.
  • To investigate the molecular pathways modulated by MST3 during oxidative stress.

Main Methods:

  • Utilized MST3-deficient cells (shMST3) and reconstituted MST3.
  • Assessed c-Jun N-terminal kinase (JNK) activation and c-Jun phosphorylation.
  • Quantified heme oxygenase-1 (HO-1) expression.
  • Employed specific inhibitors (SP600125, Zinc protoporphyrin IX) and dominant-negative constructs (JNK2, JunAA).

Main Results:

  • MST3-deficient cells exhibited resistance to H2O2, which was reversible.
  • H2O2-induced JNK activation was enhanced in MST3-deficient cells.
  • Increased c-Jun phosphorylation and HO-1 expression were observed in MST3-deficient cells, contributing to H2O2 resistance.
  • Inhibition of JNK or HO-1 pathways reversed H2O2 resistance in MST3-deficient cells.

Conclusions:

  • MST3 mediates H2O2-induced cell death by suppressing a JNK survival pathway.
  • MST3-mediated cell death involves the down-regulation of cytoprotective heme oxygenase-1 (HO-1).
  • These findings identify a novel mechanism for MST3 in regulating oxidative stress response and cell survival.

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