机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China[2]Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China内科科室外科科室神经内科泌尿外科昆明医科大学附属第一医院[3]Department of Breast, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China[4]Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has previously been reported to be overexpressed in estrogen receptor alpha (ER alpha)-positive breast tumors and to promote breast cell proliferation; however, its mechanism is unknown. In this study, we demonstrated that silencing of BCA2 by small interfering RNAs (siRNAs) in two ER alpha-positive breast cancer cell lines, MCF-7 and T47D, decreases cell proliferation and increases the protein levels of the cyclin-dependent kinase inhibitor p21(Waf/Cip1). The protein stability of p21 was negatively regulated by BCA2. BCA2 directly interacts with p21 and promotes p21 ubiquitination and proteasomal degradation. Knockdown of p21 partially rescues the cell growth arrest induced by the BCA2 siRNA. These results suggest that BCA2 promotes ER alpha-positive breast cancer cell proliferation at least partially through downregulating the expression of p21.
基金：
National Key Basic Research Program of China
(2013CB910900), National Natural Science Foundation of China (81072162,
81120108019, 81272930, and U1132605), Top Talents Program of Yunnan Province,
China (2010CI114), Science and Technological Key Project of Yunnan Province
(2012FB185), and “Western Light” Talents Training Program of Chinese Academy
of Sciences (to Q.K.). The authors have no conflicts of interest.
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
通讯作者：
通讯机构：[*1]32 Jiaochang East Rd, Kunming, Yunnan 650223, China
推荐引用方式(GB/T 7714)：
Zehua Wang,Zhi Nie,Wenlin Chen,et al.RNF115/BCA2 E3 Ubiquitin Ligase Promotes Breast Cancer Cell Proliferation through Targeting p21(Waf1/Cip1) for Ubiquitin-Mediated Degradation[J].NEOPLASIA.2013,15(9):1028-1035.doi:10.1593/neo.13678.
APA：
Zehua Wang,Zhi Nie,Wenlin Chen,Zhongmei Zhou,Qinghua Kong...&Ceshi Chen.(2013).RNF115/BCA2 E3 Ubiquitin Ligase Promotes Breast Cancer Cell Proliferation through Targeting p21(Waf1/Cip1) for Ubiquitin-Mediated Degradation.NEOPLASIA,15,(9)
MLA：
Zehua Wang,et al."RNF115/BCA2 E3 Ubiquitin Ligase Promotes Breast Cancer Cell Proliferation through Targeting p21(Waf1/Cip1) for Ubiquitin-Mediated Degradation".NEOPLASIA 15..9(2013):1028-1035
