Regulation of proteolytic cleavage of retinoid X receptor-alpha by GSK-3 beta

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	Regulation of proteolytic cleavage of retinoid X receptor-alpha by GSK-3 beta
	Gao, Weiwei ; Liu, Jie ; Hu, Mengjie ; Huang, Mingfeng ; Cai, Sisi ; Zeng, Zhiping ; Lin, Bingzhen ; Cao, Xihua ; Chen, Jiebo ; Zeng, Jin-zhang ; Zhou, Hu ; Zhang, Xiao-kun ; Liu J(刘婕) ; Ceng ZP(曾志平) ; Ceng JZ(曾锦章) ; Zhou H(周虎) ; Zhang XK(张晓坤)
刊名	http://dx.doi.org/10.1093/carcin/bgt043
	2013
关键词	GLYCOGEN-SYNTHASE KINASE-3 EPIDERMAL-GROWTH-FACTOR CELL-DEATH M-CALPAIN SIGNALING PATHWAYS NUCLEAR EXPORT CANCER PROSTATE PHOSPHORYLATION TUMORIGENESIS
英文摘要	Fundamental Research Funds for the Central Universities [2010111081]; National Natural Science Foundation of China [NSFC-91129302, NSFC- 31271453]; Tobacco-Related Disease Research Program [15FT-0243]; National Institutes of Health [CA140980, GM089927]; United States Army Medical Research and Material Command [W81XWH-11-1-0677]; We recently reported that an N-terminally truncated retinoid X receptor- (tRXR) produced in cancer cells acts to promote cancer cell growth and survival through AKT activation. However, how RXR is cleaved and how the cleavage is regulated in cancer cells remain undefined. In this study, we demonstrated that calpain II could cleave RXR protein in vitro, generating two truncated RXR products. The cleavage sites in RXR were mapped by Edman N-terminal sequencing to Gly(90)Ser(91) and Lys(118)Val(119). Transfection of the resulting cleavage product RXR/90, but not RXR/118, resulted in activation of AKT in cancer cells, similar to the effect of tRXR. In support of the role of calpain II in cancer cells, transfection of calpain II expression vector or its activation by ionomycin enhanced the production of tRXR, whereas treatment of cells with calpain inhibitors reduced the levels of tRXR. Co-immunoprecipitation assays also showed an interaction between calpain II and RXR. In studying the regulation of tRXR production, we observed that treatment of cells with lithium chloride or knockdown of glycogen synthase kinase-3 (GSK-3) significantly increased the production of tRXR. Conversely, overexpression of GSK-3 reduced tRXR expression. Furthermore, we found that the inhibitory effect of GSK-3 on tRXR production was due to its suppression of calpain II expression. Taken together, our data demonstrate that GSK-3 plays an important role in regulating tRXR production by calpain II in cancer cells, providing new insights into the development of new strategies and agents for the prevention and treatment of tRXR-related cancers.
语种	英语
出版者	OXFORD UNIV PRESS
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/89020]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Gao, Weiwei,Liu, Jie,Hu, Mengjie,et al. Regulation of proteolytic cleavage of retinoid X receptor-alpha by GSK-3 beta[J]. http://dx.doi.org/10.1093/carcin/bgt043,2013.
APA	Gao, Weiwei.,Liu, Jie.,Hu, Mengjie.,Huang, Mingfeng.,Cai, Sisi.,...&张晓坤.(2013).Regulation of proteolytic cleavage of retinoid X receptor-alpha by GSK-3 beta.http://dx.doi.org/10.1093/carcin/bgt043.
MLA	Gao, Weiwei,et al."Regulation of proteolytic cleavage of retinoid X receptor-alpha by GSK-3 beta".http://dx.doi.org/10.1093/carcin/bgt043 (2013).