RNF8 identified as a co-activator of estrogen receptor alpha promotes cell growth in breast cancer

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 (ERalpha)-positive breast cancer and underlying mechanisms have not been fully defined. Here, we have explored RNF8 as an associated partner of ERalpha in breast cancer cells, and co-activates ERalpha-mediated transactivation. Accordingly, RNF8 depletion inhibits the expression of endogenous ERalpha target genes. Interestingly, our results have demonstrated that RNF8 increases ERalpha stability at least partially if not all via triggering ERalpha 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 ERalpha. Up-regulation of ERalpha-induced transactivation by RNF8 might contribute to the promotion of breast cancer progression by allowing enhancement of ERalpha target gene expression. Our study describes RNF8 as a co-activator of ERalpha increases ERalpha stability via post-transcriptional pathway, and provides a new insight into mechanisms for RNF8 to promote cell growth of ERalpha-positive breast cancer.