Regulation of JNK signaling by GSTp

In demonstrating the relationships between glutathione S-transferase Pi expression and its association with Jun N-terminal kinase, our findings provide new insight into the regulation of stress kinases

V. Adler


Scholarcy highlights

  • Jun N-terminal kinases belong to the multi-member family of stress kinases that are activated transiently in response to UV- or X-irradiation, heat shock, osmoticDespite the significant advances in identifying the components of stress-activated protein kinases, the mechanisms underlying the regulation of JNK before and immediately after stress are not well understood
  • In cells maintained under normal growth conditions, the basal activity of JNK is low, JNK phosphorylation by upstream kinases occurs in response to growth factors and should be observed in cells proliferating under normal growth conditions
  • Our data point to an additional cellular mechanism that is involved in the regulation of JNK activity before and after stress
  • Maintaining a low basal JNK activity is believed to affect the half-life of JNK substrates, including c-Jun, ATF2 and p53, and to play a key role in maintenance of controlled cell growth
  • Forced expression of glutathione S-transferase Pi in 3T3 fibroblasts increased the degree of Jun ubiquitination and decreased Jun-mediated transactivation
  • Our results suggest that GSTp does not require transferase activity to mediate inhibition of JNK, in as much as bacterially produced GST, as well as GSTp mutated on Tyr7, which is essential for its catalytic activity, efficiently inhibited JNK enzyme and Jun transcriptional activities, respectively
  • The emerging model suggests that through its association with the Jun–Jun N-terminal kinase complex under non-stressed conditions, glutathione S-transferase Pi inhibits Jun N-terminal kinases phosphorylation and activity

Need more features? Save interactive summary cards to your Scholarcy Library.