Glutathione S-transferase P–Extracellular signal-regulated kinase protein-protein complex (GSTP1-ERK complex)

The Glutathione S-transferase P–Extracellular signal-regulated kinase (GSTP1-ERK) protein-protein complex is a regulatory assembly where GSTP1 acts as a non-enzymatic inhibitor of the ERK signaling pathway (PMID: 15661738). Under normal physiological conditions, GSTP1 binds to ERK2 (MAPK1), sequestering it and preventing its activation by MEK, thereby modulating cell growth and survival signals (UniProt P09211). In various malignancies, GSTP1 is frequently overexpressed, which leads to the excessive sequestration of ERK and the suppression of pro-apoptotic signaling, contributing to tumor progression and resistance to chemotherapy (PMID: 25613377). This complex is considered a significant therapeutic target, as disrupting the protein-protein interaction can restore ERK activity and sensitize cancer cells to apoptosis. Small molecule inhibitors like ezatiostat (TLK199) and experimental compounds such as NBD-77 have been developed to target GSTP1 or specifically disrupt its interaction with ERK to treat conditions like myelodysplastic syndrome and solid tumors (DrugBank DB04952).

Other names

GSTP1-ERK2 complexGSTP1-MAPK1 complexGSTP1-MAPK3 complexGST pi-ERK complexGSTP1-1-ERK complex

Disruption of the protein-protein interaction between GSTP1 and ERK to restore MAPK signaling and promote apoptosis in malignant cells (PMID: 25613377).