Discovery - University of Dundee - Online Publications

Library & Learning Centre

Regulation of JNK signaling by GSTp

Regulation of JNK signaling by GSTp

Research output: Contribution to journalArticle

View graph of relations


  • Victor Adler
  • Zhimin Yin
  • Serge Y. Fuchs
  • Miriam Benezra
  • Lilliam Rosario
  • Kenneth D. Tew
  • Matthew R. Pincus
  • Mohinder Sardana
  • Colin J. Henderson
  • C. Roland Wolf
  • Roger J. Davis
  • Ze'ev Ronai

Research units


Original languageEnglish
Pages (from-to)1321-1334
Number of pages14
JournalEMBO Journal
Issue number5
StatePublished - 1 Mar 1999


Studies of low basal Jun N-terminal kinase (JNK) activity in non-stressed cells led us to identify a JNK inhibitor that was purified and identified as glutathione S-transferase Pi (GSTp) and was characterized as a JNK-associated protein. UV irradiation or H2O2 treatment caused GSTp oligomerization and dissociation of the GSTp-JNK complex, indicating that it is the monomeric form of GSTp that elicits JNK inhibition. Addition of purified GSTp to the Jun-JNK complex caused a dose-dependent inhibition of JNK activity. Conversely, immunodepleting GSTp from protein extracts attenuated JNK inhibition. Furthermore, JNK activity was increased in the presence of specific GSTp inhibitors and a GSTp-derived peptide. Forced expression of GSTp decreased MKK4 and JNK phosphorylation which coincided with decreased JNK activity, increased c-Jun ubiquitination and decreased c-Jun-mediated transcription. Co-transfection of MEKK1 and GSTp restored MKK4 phosphorylation but did not affect GSTp inhibition of JNK activity, suggesting that the effect of GSTp on JNK is independent of the MEKK1-MKK4 module. Mouse embryo fibroblasts from GSTp-null mice exhibited a high basal level of JNK activity that could be reduced by forced expression of GSTp cDNA, In demonstrating the relationships between GSTp expression and its association with JNK, our findings provide new insight into the regulation of stress kinases.


Library & Learning Centre

Contact | Accessibility | Policy