Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells
| العنوان: | Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells |
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| المؤلفون: | Chuan-Le Xiao, Li-Jun Bi, Feng Ge, Xin-Feng Yin, Sheng-Ce Tao, Sheng Xiong, Liping Li, Hai-Tao Jia, Chun-Hua Lu, Qing-Yu He |
| المصدر: | PLoS ONE, Vol 5, Iss 9 (2010) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Proteomics, Proteasome Endopeptidase Complex, Chemical Biology/Protein Chemistry and Proteomics, Science, Down-Regulation, Stathmin, Cell Biology/Cell Signaling, Bortezomib, immune system diseases, Stable isotope labeling by amino acids in cell culture, Cell Line, Tumor, hemic and lymphatic diseases, medicine, Humans, Protease Inhibitors, Phosphorylation, Multiple myeloma, Biochemistry/Experimental Biophysical Methods, Multidisciplinary, biology, Hematology/Myeloma, Phosphoproteomics, medicine.disease, Phosphoproteins, Boronic Acids, Cell biology, Proteasome, Biophysics/Protein Chemistry and Proteomics, Pyrazines, Proteasome inhibitor, biology.protein, Medicine, Biotechnology/Protein Chemistry and Proteomics, Biochemistry/Drug Discovery, Multiple Myeloma, Proteasome Inhibitors, medicine.drug, Research Article |
| الوصف: | BackgroundThe proteasome inhibitor bortezomib represents an important advance in the treatment of multiple myeloma (MM). Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood.Methodology/principal findingsWe investigated the differential phosphoproteome upon proteasome inhibition by using stable isotope labeling by amino acids in cell culture (SILAC) in combination with phosphoprotein enrichment and LC-MS/MS analysis. In total 233 phosphoproteins were identified and 72 phosphoproteins showed a 1.5-fold or greater change upon bortezomib treatment. The phosphoproteins with expression alterations encompass all major protein classes, including a large number of nucleic acid binding proteins. Site-specific phosphopeptide quantitation revealed that Ser38 phosphorylation on stathmin increased upon bortezomib treatment, suggesting new mechanisms associated to bortezomib-induced apoptosis in MM cells. Further studies demonstrated that stathmin phosphorylation profile was modified in response to bortezomib treatment and the regulation of stathmin by phosphorylation at specific Ser/Thr residues participated in the cellular response induced by bortezomib.Conclusions/significanceOur systematic profiling of phosphorylation changes in response to bortezomib treatment not only advanced the global mechanistic understanding of the action of bortezomib on myeloma cells but also identified previously uncharacterized signaling proteins in myeloma cells. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8462d815a59759bba1e34715d083c47 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20927383/?tool=EBI |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b8462d815a59759bba1e34715d083c47 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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