Glutathione transferase Omega 1-1 (GSTO1-1) modulates Akt and MEK1/2 signaling in human neuroblastoma cell SH-SY5Y

Chonticha Saisawang, Jantana Wongsantichon, Robert C. Robinson, Albert J. Ketterman

Research output: Contribution to journalArticle

Abstract

In the human neuroblastoma SH-SY5Y cell line, the glutathione transferase Omega 1-1 (GSTO1-1) appears to modulate Akt and MEK1/2 kinase activation. We observed a glutathionylation modification was involved in the activation of Akt but not MEK1/2. With the specific GSTO1-1 inhibitor ML175, we show the enzyme activity of GSTO1-1 is important for modulation as the inhibited GSTO1-1 allowed activation of both Akt and MEK1/2. The inhibition of GSTO1-1 showed a similar extent of activation of Akt and MEK1/2 as treatment by the endotoxin lipopolysaccharide. The GSTO1-1 also either directly interacts with Akt and MEK1/2 or interacts with a protein complexed with Akt and MEK1/2 as both kinases coimmunoprecipitated with GSTO1-1. The results suggest that GSTO1-1 enzyme activity inhibits the activation of these two kinases to maintain basal levels. The possible regulation by GSTO1-1 is of interest as both kinases have hundreds of potential downstream targets that are known to have contributions to various cellular processes including survival, growth, proliferation, and metabolism.

Original languageEnglish
Pages (from-to)588-595
Number of pages8
JournalProteins: Structure, Function and Bioinformatics
Volume87
Issue number7
DOIs
Publication statusPublished - Jul 2019

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Keywords

  • Akt/PKB
  • glutathione transferase (GST)
  • glutathionylation
  • MEK1/2
  • ML175

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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