Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells

doi:10.1021/pr4012848

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	Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells
	Wen, Donghua 2; Xu, Zhijian1 ; Xia, Li 2; Liu, Xinyi 2; Tu, Yaoyao 2; Lei, Hu 2; Wang, Weiwei 2; Wang, Tongdan 2; Song, Lili 2; Ma, Chunmin 2
刊名	JOURNAL OF PROTEOME RESEARCH
	2014-08
卷号	13 期号:8 页码:3571-3582
关键词	SUMOylation SENP SENP inhibitor chemical proteomics quantitative proteomics SILAC spliceosome USP39
ISSN号	1535-3893
DOI	10.1021/pr4012848
文献子类	Article
英文摘要	Sentrin/SUMO (small ubiquitin-like modifier)-specific proteases (SENPs) have been implicated in the development of prostate cancer. However, due to the low abundance of SUMO-modified proteins and high activity of SENPs, the SUMO substrates affected by SENPs in prostate cancer cells are largely unknown. Here, we identified SI2, a novel cell-permeable SENP-specific inhibitor, by high-throughput screening. Using SI2 as a way of inhibiting the activity of SENPs and the SUMO stably transfected PC3 cells as a prostate cancer model, in combination with the stable isotope labeling with amino acids (SILAC) quantitative proteomic technique, we identified more than 900 putative target proteins of SUMO, in which 231 proteins were further subjected to bioinformatic analysis. In the highly enriched spliceosome pathway, we validated that USP39, HSPA1A, and HSPA2 were novel target proteins of SUMO. Furthermore, we demonstrated that K6, K16, K29, K51, and K73 were the SUMOylation sites of USP39. Mutation of these SUMO modification sites of USP39 further promoted the proliferation-enhancing effect of USP39 on prostate cancer cells. This study provides the SUMOproteome of PC3 cells and reveals that SUMOylation of spliceosome factors may be implicated in the pathogenesis of prostate cancer. Optimization of SI2 for isotype-specific SENP inhibitors warrants further investigation.
资助项目	National Basic Research Program of China (973 Program)[2010CB912104] ; National Basic Research Program of China (973 Program)[2009CB149104] ; National Natural Science Foundation of China[91013008] ; National Natural Science Foundation of China[91313303] ; National Natural Science Foundation of China[31100980] ; National Natural Science Foundation of China[81272886] ; Science and Technology Committee of Shanghai[11JC1406500] ; Ministry of Science and Technology[2012AA01A305] ; SMC Program of Shanghai Jiao Tong University[00000000]
WOS关键词	U4/U6-CENTER-DOT-U5 TRI-SNRNP ; SMALL-MOLECULE INHIBITORS ; SUMO-SPECIFIC PROTEASE-1 ; IN-VITRO ; PROTEINS ; DATABASE ; PROGRESSION ; MECHANISMS ; DOCKING ; PROBES
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000339983600008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276965]
专题	药物发现与设计中心
通讯作者	Chen, Guoqiang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol,Natl Minist Educ, Chem Biol Div,Shanghai Univ E Inst,Key Lab Cell D, Shanghai 200025, Peoples R China;
推荐引用方式 GB/T 7714	Wen, Donghua,Xu, Zhijian,Xia, Li,et al. Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells[J]. JOURNAL OF PROTEOME RESEARCH,2014,13(8):3571-3582.
APA	Wen, Donghua.,Xu, Zhijian.,Xia, Li.,Liu, Xinyi.,Tu, Yaoyao.,...&Wu, Yingli.(2014).Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells.JOURNAL OF PROTEOME RESEARCH,13(8),3571-3582.
MLA	Wen, Donghua,et al."Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells".JOURNAL OF PROTEOME RESEARCH 13.8(2014):3571-3582.