Glutathione S-transferase P–c-Jun N-terminal kinase complex (GSTP1–JNK complex)

The Glutathione S-transferase P–c-Jun N-terminal kinase (GSTP1–JNK) complex is a regulatory protein-protein interaction that serves as a key switch in the cellular stress response and apoptotic pathways (Adler et al., 1999, EMBO J). In its basal state, GSTP1 binds to the C-terminal region of JNK, inhibiting its phosphorylation and preventing the activation of downstream pro-apoptotic signaling (Laborde, 2010, Anticancer Agents Med Chem). This sequestration is particularly relevant in oncology, as many tumors overexpress GSTP1 to suppress JNK-mediated apoptosis, thereby contributing to chemoresistance and tumor survival (Tew, 2007, Free Radic Biol Med). Therapeutic targeting of this complex focuses on small molecules that disrupt the GSTP1–JNK interaction or inhibit GSTP1's enzymatic activity, such as Ezatiostat (TLK199) and NBD-18 (Zhang et al., 2014, Methods Enzymol). By releasing JNK from the complex, these drugs restore the cell's ability to undergo programmed cell death in response to stress or chemotherapy. Consequently, the GSTP1–JNK complex represents a significant target for sensitizing resistant tumors and treating hematological malignancies like myelodysplastic syndrome (Ruscoe et al., 2001, J Pharmacol Exp Ther).

Other names

GSTP1-JNK1 complexGST pi-JNK complexGlutathione S-transferase pi 1–c-Jun N-terminal kinase complexGSTP1-MAPK8 complex

Disruption of the protein-protein interaction to release and activate JNK, promoting apoptosis in cancer cells.