New Insights into the Mechanism of JNK1 Inhibition by Glutathione Transferase P1-1

Contrary to what previous studies suggest, we found that GSTP1-1 is able to form a complex with the unphosphorylated and inactive JNK1α2 isoform, even in the absence of the substrate

Anastasia De Luca

2012

Key concepts

Scholarcy highlights

  • The role played by glutathione transferase P1-1 in modulating the c-Jun N-terminal kinase pathway has been extensively investigated using JNK isoforms known to exert opposite effects in the cells
  • Contrary to what previous studies suggest, we found that GSTP1-1 is able to form a complex with the unphosphorylated and inactive JNK1α2 isoform, even in the absence of the substrate
  • The complex strongly reduced the extent of activation of JNK1α2 and preserved GSTP1-1 from inactivation
  • Glutathione exerted a negative effect on the affinity of GSTP1-1 for JNK1α2, suggesting that the intracellular levels of this thiol may allow a fine-tuning of the MAPK signaling pathway
  • We found that the adduct formed by GSH and the strong GSTP1-1 inhibitor NBDHEX abolishes the interaction between GSTP1-1 and JNK1α2
  • These data confirm and extend at the molecular level previous evidence obtained in tumor cell lines

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