Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells.
<h4>Background</h4>The 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...
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doaj-89edd93f68fc4e119593f13c6a7b02da2021-03-04T02:18:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-015910.1371/journal.pone.0013095Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells.Feng GeChuan-Le XiaoLi-Jun BiSheng-Ce TaoSheng XiongXin-Feng YinLi-Ping LiChun-Hua LuHai-Tao JiaQing-Yu He<h4>Background</h4>The 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.<h4>Methodology/principal findings</h4>We 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.<h4>Conclusions/significance</h4>Our 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20927383/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Feng Ge Chuan-Le Xiao Li-Jun Bi Sheng-Ce Tao Sheng Xiong Xin-Feng Yin Li-Ping Li Chun-Hua Lu Hai-Tao Jia Qing-Yu He |
spellingShingle |
Feng Ge Chuan-Le Xiao Li-Jun Bi Sheng-Ce Tao Sheng Xiong Xin-Feng Yin Li-Ping Li Chun-Hua Lu Hai-Tao Jia Qing-Yu He Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells. PLoS ONE |
author_facet |
Feng Ge Chuan-Le Xiao Li-Jun Bi Sheng-Ce Tao Sheng Xiong Xin-Feng Yin Li-Ping Li Chun-Hua Lu Hai-Tao Jia Qing-Yu He |
author_sort |
Feng Ge |
title |
Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells. |
title_short |
Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells. |
title_full |
Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells. |
title_fullStr |
Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells. |
title_full_unstemmed |
Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells. |
title_sort |
quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-09-01 |
description |
<h4>Background</h4>The 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.<h4>Methodology/principal findings</h4>We 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.<h4>Conclusions/significance</h4>Our 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. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20927383/?tool=EBI |
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