Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics

Abstract Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteom...

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Autores principales:	Qingdi Quentin Li, Jian-Jiang Hao, Zheng Zhang, L. Spencer Krane, Kai H. Hammerich, Thomas Sanford, Jane B. Trepel, Len Neckers, Piyush K. Agarwal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d315dc00c8384dfc8ae699ecec61f833
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spelling	oai:doaj.org-article:d315dc00c8384dfc8ae699ecec61f8332021-12-02T16:07:02ZProteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics10.1038/s41598-017-00143-62045-2322https://doaj.org/article/d315dc00c8384dfc8ae699ecec61f8332017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00143-6https://doaj.org/toc/2045-2322Abstract Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteomic study that evaluates alterations in protein expression and histone post-translational modifications (PTMs) in bladder carcinoma in response to HSP90 inhibition. We show that 5 HSP90 inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) potently inhibited the proliferation of bladder cancer 5637 cells in a dose- and time-dependent manner. Our proteomic study quantified 518 twofold up-regulated and 811 twofold down-regulated proteins common to both AUY922 and ganetespib treatment. Bioinformatic analyses revealed that those differentially expressed proteins were involved in multiple cellular processes and enzyme-regulated signaling pathways, including chromatin modifications and cell death-associated pathways. Furthermore, quantitative proteome studies identified 14 types of PTMs with 93 marks on the core histones, including 34 novel histone marks of butyrylation, citrullination, 2-hydroxyisobutyrylation, methylation, O-GlcNAcylation, propionylation, and succinylation in AUY922- and ganetespib-treated 5637 cells. Together, this study outlines the association between proteomic changes and histone PTMs in response to HSP90 inhibitor treatment in bladder carcinoma cells, and thus intensifies the understanding of HSP90 inhibition-mediated bladder cancer therapeutics.Qingdi Quentin LiJian-Jiang HaoZheng ZhangL. Spencer KraneKai H. HammerichThomas SanfordJane B. TrepelLen NeckersPiyush K. AgarwalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-20 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qingdi Quentin Li Jian-Jiang Hao Zheng Zhang L. Spencer Krane Kai H. Hammerich Thomas Sanford Jane B. Trepel Len Neckers Piyush K. Agarwal Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
description	Abstract Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteomic study that evaluates alterations in protein expression and histone post-translational modifications (PTMs) in bladder carcinoma in response to HSP90 inhibition. We show that 5 HSP90 inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) potently inhibited the proliferation of bladder cancer 5637 cells in a dose- and time-dependent manner. Our proteomic study quantified 518 twofold up-regulated and 811 twofold down-regulated proteins common to both AUY922 and ganetespib treatment. Bioinformatic analyses revealed that those differentially expressed proteins were involved in multiple cellular processes and enzyme-regulated signaling pathways, including chromatin modifications and cell death-associated pathways. Furthermore, quantitative proteome studies identified 14 types of PTMs with 93 marks on the core histones, including 34 novel histone marks of butyrylation, citrullination, 2-hydroxyisobutyrylation, methylation, O-GlcNAcylation, propionylation, and succinylation in AUY922- and ganetespib-treated 5637 cells. Together, this study outlines the association between proteomic changes and histone PTMs in response to HSP90 inhibitor treatment in bladder carcinoma cells, and thus intensifies the understanding of HSP90 inhibition-mediated bladder cancer therapeutics.
format	article
author	Qingdi Quentin Li Jian-Jiang Hao Zheng Zhang L. Spencer Krane Kai H. Hammerich Thomas Sanford Jane B. Trepel Len Neckers Piyush K. Agarwal
author_facet	Qingdi Quentin Li Jian-Jiang Hao Zheng Zhang L. Spencer Krane Kai H. Hammerich Thomas Sanford Jane B. Trepel Len Neckers Piyush K. Agarwal
author_sort	Qingdi Quentin Li
title	Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
title_short	Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
title_full	Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
title_fullStr	Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
title_full_unstemmed	Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
title_sort	proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d315dc00c8384dfc8ae699ecec61f833
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Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics

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