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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/89edd93f68fc4e119593f13c6a7b02da
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spelling	oai:doaj.org-article:89edd93f68fc4e119593f13c6a7b02da2021-11-18T07:03:49ZQuantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells.1932-620310.1371/journal.pone.0013095https://doaj.org/article/89edd93f68fc4e119593f13c6a7b02da2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20927383/?tool=EBIhttps://doaj.org/toc/1932-6203<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.Feng GeChuan-Le XiaoLi-Jun BiSheng-Ce TaoSheng XiongXin-Feng YinLi-Ping LiChun-Hua LuHai-Tao JiaQing-Yu HePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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.
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.
format	article
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
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)
publishDate	2010
url	https://doaj.org/article/89edd93f68fc4e119593f13c6a7b02da
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Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells.

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