Abstract
Transitional cell carcinoma (TCC) of urinary bladder belongs to glutathione S-transferase P1 (GSTP1) overexpressing tumors. Upregulated GSTP1 in TCC is related to apoptosis inhibition. This antiapoptotic effects of GSTP1 might be mediated through protein:protein interaction with c-Jun NH(2) -terminal kinase (JNK). Herein, we analyzed whether a direct link between GSTP1 and JNK exists in TCC. The presence of GSTP1/JNK complexes was analyzed by immunoprecipitation and Western blotting in 20 TCC specimens, obtained after surgery. Co-localization of GSTP1 and JNK was also investigated in the 5637 TCC cell line by immunofluorescence confocal microscopy. By means of immunoprecipitation we show for the first time the presence of GSTP1/JNK complexes in all TCC samples studied. A co-localization of GSTP1 and JNK was also demonstrated in the 5637 TCC cell line by means of confocal microscopy. Protein-protein interactions, together with co-localization between GSTP1 and JNK provide evidence that GSTP1 most probably inhibits apoptosis in TCC cells by non-covalent binding to JNK.
Highlights
The glutathione transferases are a multigene family of isozymes that catalyze the nucleophilic attack of the sulfur atom of glutathione on electrophilic groups of substrate molecules (Hayes and Strange, 2000)
glutathione S-transferase P1 (GSTP1) is overexpressed in many tumors, including transitional cell carcinoma (TCC) of urinary bladder, where its activity and expression correlate with tumor stage and grade (Berendsen et al, 1997; Townsend and Tew, 2003; Simic et al, 2005)
Redox-active monomeric GSTP1 subunits inhibit c-Jun NH2-terminal kinase (JNK), an enzyme that triggers the apoptotic cascade in several cancer cell lines (Wang et al, 2001)
Summary
The glutathione transferases are a multigene family of isozymes that catalyze the nucleophilic attack of the sulfur atom of glutathione on electrophilic groups of substrate molecules (Hayes and Strange, 2000). GSTP1 is overexpressed in many tumors, including transitional cell carcinoma (TCC) of urinary bladder, where its activity and expression correlate with tumor stage and grade (Berendsen et al, 1997; Townsend and Tew, 2003; Simic et al, 2005). Redox-active monomeric GSTP1 subunits inhibit c-Jun NH2-terminal kinase (JNK), an enzyme that triggers the apoptotic cascade in several cancer cell lines (Wang et al, 2001).
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