COP1 and GSK3 beta Cooperate to Promote c-Jun Degradation and Inhibit Breast Cancer Cell Tumorigenesis

CORC > 厦门大学 > 生命科学－已发表论文

	COP1 and GSK3 beta Cooperate to Promote c-Jun Degradation and Inhibit Breast Cancer Cell Tumorigenesis
	Shao, Jing ; Teng, Yong ; Padia, Ravi ; Hong, Sungguan ; Noh, Hyangsoon ; Xie, Xiayang ; Mumm, Jeff S. ; Dong, Zheng ; Ding, Han-Fei ; Cowell, John ; Kim, Jaejik ; Han, Jiahuai ; Huang, Shuang ; Han JH(韩家淮)
刊名	http://dx.doi.org/10.1593/neo.13966
	2013
关键词	UBIQUITIN LIGASE MEDIATED DEGRADATION NEGATIVE REGULATOR TUMOR-SUPPRESSOR AP-1 PHOSPHORYLATION OVEREXPRESSION METASTASIS ACTIVATION EXPRESSION
英文摘要	National Institutes of Health [HL083335]; Shanghai Eastern Scholar Fund; E-Institutes of Shanghai Municipal Education Commission [E03008]; High abundance of c-Jun is detected in invasive breast cancer cells and aggressive breast tumor malignancies. Here, we demonstrate that a major cause of high c-Jun abundance in invasive breast cancer cells is prolonged c-Jun protein stability owing to poor poly-ubiquitination of c-Jun. Among the known c-Jun-targeting E3 ligases, we identified constitutive photomorphogenesis protein 1 (COP1) as an E3 ligase responsible for c-Jun degradation in less invasive breast cancer cells because depletion of COP1 reduced c-Jun poly-ubiquitination leading to the stabilization of c-Jun protein. In a panel of breast cancer cell lines, we observed an inverse association between the levels of COP1 and c-Jun. However, overexpressing COP1 alone was unable to decrease c-Jun level in invasive breast cancer cells, indicating that efficient c-Jun protein degradation necessitates an additional event. Indeed, we found that glycogen synthase kinase 3 (GSK3) inhibitors elevated c-Jun abundance in less invasive breast cancer cells and that GSK3 beta nonphosphorylable c-Jun-T239A mutant displayed greater protein stability and poorer poly-ubiquitination compared to the wild-type c-Jun. The ability of simultaneously enforced expression of COP1 and constitutively active GSK3 beta to decrease c-Jun abundance in invasive breast cancer cells allowed us to conclude that c-Jun is negatively regulated through the coordinated action of COP1 and GSK3 beta. Importantly, co-expressing COP1 and active GSK3 beta blocked in vitro cell growth/migration and in vivo metastasis of invasive breast cancer cells. Gene expression profiling of breast tumor specimens further revealed that higher COP1 expression correlated with better recurrence-free survival. Our study supports the notion that COP1 is a suppressor of breast cancer progression.
语种	英语
出版者	NEOPLASIA PRESS
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90689]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Shao, Jing,Teng, Yong,Padia, Ravi,et al. COP1 and GSK3 beta Cooperate to Promote c-Jun Degradation and Inhibit Breast Cancer Cell Tumorigenesis[J]. http://dx.doi.org/10.1593/neo.13966,2013.
APA	Shao, Jing.,Teng, Yong.,Padia, Ravi.,Hong, Sungguan.,Noh, Hyangsoon.,...&韩家淮.(2013).COP1 and GSK3 beta Cooperate to Promote c-Jun Degradation and Inhibit Breast Cancer Cell Tumorigenesis.http://dx.doi.org/10.1593/neo.13966.
MLA	Shao, Jing,et al."COP1 and GSK3 beta Cooperate to Promote c-Jun Degradation and Inhibit Breast Cancer Cell Tumorigenesis".http://dx.doi.org/10.1593/neo.13966 (2013).