RNF115/BCA2 E3 Ubiquitin Ligase Promotes Breast Cancer Cell Proliferation through Targeting p21Waf1/Cip1 for Ubiquitin-Mediated Degradation
RNF115/BCA2 E3 Ubiquitin Ligase Promotes Breast Cancer Cell Proliferation through Targeting p21Waf1/Cip1 for Ubiquitin-Mediated Degradation
复制标题
RNF115/BCA2 E3 泛素连接酶通过靶向 p21Waf1/Cip1 进行泛素介导的降解来促进乳腺癌细胞增殖
DOI：
10.1593/neo.13678
复制
发表时间：
2013-09-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Ceshi
中科院分区：
文献类型：
--
作者：
Wang, Zehua;Nie, Zhi;Chen, Ceshi
E3泛素连接酶RING指蛋白115（RNF 115），也称为乳腺癌相关基因2（BCA 2），先前已报道在雌激素受体α（ER α）阳性乳腺肿瘤中过表达，并促进乳腺细胞增殖;然而，其机制尚不清楚。在这项研究中，我们证明了在两种ER α阳性乳腺癌细胞系MCF-7和T47 D中通过小干扰RNA（siRNA）沉默BCA 2，降低细胞增殖并增加细胞周期蛋白依赖性激酶抑制剂p21（Waf/Cip 1）的蛋白水平。BCA 2负调控p21蛋白的稳定性。BCA 2直接与p21相互作用，促进p21泛素化和蛋白酶体降解。p21的敲低部分地挽救了由BCA 2 siRNA诱导的细胞生长停滞。这些结果表明，BCA 2促进ER α阳性乳腺癌细胞增殖至少部分通过下调p21的表达。
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.