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Co-localization of GSTP1 and JNK in transitional cell carcinoma of urinary bladder
Marija Pljesa-Ercegovac1, Ana Savic-Radojevic, Tamara Kravic-Stevovic
1Faculty of Medicine, Institute of Medical and Clinical Biochemistry, University of Belgrade, Belgrade Serbia.
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.
Insights
Glutathione S-transferase P1 (GSTP1) overexpression in bladder cancer (TCC) inhibits apoptosis by interacting with c-Jun NH2-terminal kinase (JNK). This study confirms a direct GSTP1-JNK complex in TCC, revealing a novel therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Transitional cell carcinoma (TCC) of the urinary bladder frequently overexpresses glutathione S-transferase P1 (GSTP1).
- Upregulated GSTP1 is associated with inhibited apoptosis in TCC.
- GSTP1's antiapoptotic role may involve interaction with c-Jun NH2-terminal kinase (JNK).
Purpose of the Study:
- To investigate the direct protein-protein interaction between GSTP1 and JNK in TCC.
- To determine if GSTP1-JNK complexes are present in human TCC specimens.
- To elucidate the mechanism of GSTP1-mediated apoptosis inhibition in TCC.
Main Methods:
- Immunoprecipitation and Western blotting were used to detect GSTP1/JNK complexes in 20 TCC surgical specimens.
- Immunofluorescence confocal microscopy was employed to assess the co-localization of GSTP1 and JNK in the 5637 TCC cell line.
Main Results:
- The study provides the first evidence of GSTP1/JNK complexes in all analyzed TCC samples.
- Co-localization of GSTP1 and JNK was confirmed in the 5637 TCC cell line.
- These findings indicate a direct interaction between GSTP1 and JNK within TCC cells.
Conclusions:
- GSTP1 directly interacts with JNK in TCC.
- This interaction likely underlies GSTP1's role in inhibiting apoptosis in TCC.
- Targeting the GSTP1-JNK interaction may offer a novel therapeutic strategy for TCC.
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