Estrogen/ER signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ER to potentiate ER target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ER, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ER transcriptional activity and concomitantly enhances ER acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ER responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ER and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer.
基金：
National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872131, 31671415, 81471000]; Shanghai Committee of Science and TechnologyShanghai Science & Technology Committee [15410724200]
第一作者机构：[1]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Fac Med Lab Sci, Shanghai, Peoples R China[2]Shanghai Jiao Tong Univ, Fac Basic Med, Tongren Hosp, Hongqiao Inst Med,Sch Med, Shanghai, Peoples R China[3]Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Clin Lab, Shanghai, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[2]Shanghai Jiao Tong Univ, Fac Basic Med, Tongren Hosp, Hongqiao Inst Med,Sch Med, Shanghai, Peoples R China[5]Lanling Peoples Hosp, Dept Gynecol, Lanling, Shandong, Peoples R China[7]Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cellular Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai, Peoples R China
推荐引用方式(GB/T 7714)：
Xu Beihui,Li Qi,Chen Ning,et al.The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ER alpha and enhances ER alpha target gene expression in breast cancer cells[J].NUCLEIC ACIDS RESEARCH.2019,47(5):2322-2335.doi:10.1093/nar/gky1306.
APA：
Xu, Beihui,Li, Qi,Chen, Ning,Zhu, Chunxiao,Meng, Qingrong...&Hou, Zhaoyuan.(2019).The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ER alpha and enhances ER alpha target gene expression in breast cancer cells.NUCLEIC ACIDS RESEARCH,47,(5)
MLA：
Xu, Beihui,et al."The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ER alpha and enhances ER alpha target gene expression in breast cancer cells".NUCLEIC ACIDS RESEARCH 47..5(2019):2322-2335
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