title: RNF8 identified as a co-activator of estrogen receptor α promotes cell growth in breast cancer.
abstract: The ring finger protein 8 (RNF8), a key component of protein complex crucial for DNA-damage response, consists of a forkhead-associated (FHA) domain and a really interesting new gene (RING) domain that enables it to function as an E3 ubiquitin ligase. However, the biological functions of RNF8 in estrogen receptor α (ERα)-positive breast cancer and underlying mechanisms have not been fully defined. Here, we have explored RNF8 as an associated partner of ERα in breast cancer cells, and co-activates ERα-mediated transactivation. Accordingly, RNF8 depletion inhibits the expression of endogenous ERα target genes. Interestingly, our results have demonstrated that RNF8 increases ERα stability at least partially if not all via triggering ERα monoubiquitination. RNF8 functionally promotes breast cancer cell proliferation. RNF8 is highly expressed in clinical breast cancer samples and the expression of RNF8 positively correlates with that of ERα. Up-regulation of ERα-induced transactivation by RNF8 might contribute to the promotion of breast cancer progression by allowing enhancement of ERα target gene expression. Our study describes RNF8 as a co-activator of ERα increases ERα stability via post-transcriptional pathway, and provides a new insight into mechanisms for RNF8 to promote cell growth of ERα-positive breast cancer.
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Hongmiao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Renlong
authors.initials: R
authors.lastname: Zou
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Rijiao
authors.initials: R
authors.lastname: Cong
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110003, China.
authors.forename: Da
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110003, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110003, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Guangqi
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Min
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China. Electronic address: zhaoyue@mail.cmu.edu.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; C486521:RNF8 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Breast cancer; Co-activator; Estrogen receptor α; RNF8; Ubiquitination