Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1863, Issue 6, Pages 1615-1628Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2017.02.011
Keywords
RNF8; Co-activator; Estrogen receptor alpha; Ubiquitination; Breast cancer
Funding
- 973 Program Grant from the Ministry of Science and Technology of China [2013CB945201]
- National Natural Science Foundation of China [31171259, 31271364, 31401115, 81402130, 81502438]
- Ministry of Education fund innovation team [IRT 13101]
- Ministry of Education, Science and Technology research [213008A]
- National Science Foundation of Liaoning Province, China [2013021095]
- Fok Ying Tung Education Foundation [151039]
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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 alpha (ER alpha)-positive breast cancer and underlying mechanisms have not been fully defined. Here, we have explored RNF8 as an associated partner of ER alpha in breast cancer cells, and co-activates ER alpha-mediated transactivation. Accordingly, RNF8 depletion inhibits the expression of endogenous ER alpha target genes. Interestingly, our results have demonstrated that RNF8 increases ER alpha stability at least partially if not all via triggering ER alpha 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 ER alpha. Up-regulation of ER alpha-induced transactivation by RNF8 might contribute to the promotion of breast cancer progression by allowing enhancement of ER alpha target gene expression. Our study describes RNF8 as a co-activator of ER alpha increases ER alpha stability via post-transcriptional pathway, and provides a new insight into mechanisms for RNF8 to promote cell growth of ER alpha-positive breast cancer. (C) 2017 Elsevier B.V. All rights reserved.
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