Matrin 3 co-immunoprecipitates with the heat shock proteins glucose-regulated protein 78 (GRP78), GRP75 and glutathione S-transferase π isoform 2 (GSTπ2) in thymoma cells.
Here, we report evidence that matrin 3 (MATR3), a highly conserved inner nuclear matrix phosphoprotein, whose function is largely unknown, interacts specifically with the heat shock proteins glucose-regulated protein 78 (GRP78), GRP75 and glutathione S-transferase π isoform 2 (GSTπ2). Using immunoprecipitation experiments of lysates obtained from control and tributyltin oxide (TBTO)-treated thymoma cell line (EL4), we identified MATR3 and its partners by MS/MS analysis and confirmed by immunoblot. We also show that MATR3 undergoes degradation as reported before and that this cleavage process, which is inhibited by the broad-spectrum caspase inhibitor, z-VAD-FMK, is more marked in TBTO-treated cells. Further, we found that the heat shock protein glucose-regulated protein 78 was downregulated in the TBTO-treated cells. The GRP78 protein is known to protect cells from apoptosis by complexing with procaspase 7 thereby preventing caspase activation cascade. By immunoblot analysis, we found that the levels of procaspases-3 and -7 were lower in TBTO-treated cells; in contrast, the level of p20, the active form of caspase 3, was relatively higher in the treated cells compared to that of control cells. We propose that the TBTO-mediated downregulation of GRP78 triggers the caspase cascade pathway leading to MATR3 degradation.
National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands; Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: Ahmedosman_95@hotmail.com.
Ahmed M
AM
Osman
National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands; Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Henk
H
van Loveren
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013945:Thymoma; D014220:Trialkyltin Compounds / Q000494:pharmacology
D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins; D014220:Trialkyltin Compounds; C018551:glucose-regulated proteins; C573692:matrin-3 protein, mouse; C005961:bis(tri-n-butyltin)oxide; D051549:Glutathione S-Transferase pi; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7
Immunoprecipitation; Matrin 3; Protein-interactions; Proteolysis; Proteomics; TBTO