E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation

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	E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation
	Zhi X 1,4; Zhao D 1,4; Wang ZH 1; Zhou ZM 1; Wang CY 1,2; Chen WL 3; Liu R[]1; Chen CS[]1
刊名	CANCER RESEARCH
	2013
卷号	73 期号:1 页码:385-394
通讯作者	liurong@mail.kiz.ac.cn ; liurong@mail.kiz.ac.cn
合作状况	其它
英文摘要	To identify novel oncogenic E3 ubiquitin ligases as anticancer targets, we screened an E3 ubiquitin ligase siRNA library containing siRNA pools against 555 individual E3s using the sulphorhodamine B assay in the MDA-MB-231 breast cancer cell line and the PC3 prostate cancer cell line. RNF126 was identified and validated as a candidate from this screening. Knockdown of RNF126 dramatically decreased cell viability in these cancer cell lines. Consistently, RNF126 knockdown delayed cell-cycle G(1)-S progression and decreased cell proliferation. Using protein array analysis we found that RNF126 silencing increased cell-cycle dependent kinase inhibitor p21(cip) protein levels in both MDA-MB-231 and PC3. Knockdown of RNF126 stabilized the p21 protein rather than increased p21 mRNA levels. We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner. RNF126 knockdown induced loss of cell viability in MDA-MB-231 and PC-3 can be partially rescued by depletion of p21. RNF126 stable knockdown in PC3 inhibited tumor growth in SCID mice. Finally, we found that RNF126 is highly expressed in a subset of breast cancer cell lines and negatively correlated with p21 expression levels. These findings suggest that RNF126 promotes cancer cell proliferation by targeting p21 for ubiquitin-mediated degradation. RNF126 could be a novel therapeutic target in breast and prostate cancers.
收录类别	SCI
资助信息	This study was supported by National Nature Science Foundation of China (81072162, 81120108019, and U1132605) , Top Talents Program of Yunnan Province, China (2010CI114), and Strategic Priority Research Program of the Chinese Academy of Sciences，Stem Cell and Regenerative Medicine Research (XDA01040406).
语种	英语
WOS记录号	WOS:000313019800038
公开日期	2013-03-08
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/7273]
专题	昆明动物研究所_肿瘤生物学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Key Laboratory of Animal Models and Human DiseaseMechanismsofChineseAcademyofSciences&YunnanProvince, Kunming Institute of Zoology 2.The Department of Pathology of the 1 st affiliated Hospital of Kunming Medical University 3.The Department of Breast of the 3 rd affiliated Hospital of Kunming Medical University, Kunm- ing,Yunnan,China 4.The Center for Cel lBiology and Cancer Research, Albany Medical College, Albany, New York
推荐引用方式 GB/T 7714	Zhi X,Zhao D,Wang ZH,et al. E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation[J]. CANCER RESEARCH,2013,73(1):385-394.
APA	Zhi X.,Zhao D.,Wang ZH.,Zhou ZM.,Wang CY.,...&Chen CS[*].(2013).E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation.CANCER RESEARCH,73(1),385-394.
MLA	Zhi X,et al."E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation".CANCER RESEARCH 73.1(2013):385-394.