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.

RNF168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT1

“…Quite a few RING protein family members have been shown to modulate nuclear receptors and transcriptional factors via transcriptional or post‐translational regulation . For example, RNF8 and RNF31 were shown to promote oestrogen receptor alpha protein stability via facilitating ER alpha mono‐ubiquitination . RNF168 as a family of RING finger proteins, was firstly discovered as an ubiquitin‐binding domain protein .…”

“…Quite a few RING protein family members have been shown to modulate nuclear receptors and transcriptional factors via transcriptional or post-translational regulation. [25][26][27][28][29] For example, RNF8…”

“…and RNF31 were shown to promote oestrogen receptor alpha protein stability via facilitating ER alpha mono-ubiquitination. 27,29,30 RNF168 as a family of RING finger proteins, was firstly discovered as an ubiquitin-binding domain protein. 10 Further studies demonstrated that RNF168 plays an essential role of ubiquitination modification in DDR.…”

RNF168 facilitates oestrogen receptor ɑ transcription and drives breast cancer proliferation

“…Among the hundreds of putative E3 in humans, the really interesting new gene (RING) finger protein family has attracted the research attention due the uncommon ubiquitination mechanisms and involvement in chromatin modulations . Interestingly, quite a few RING finger proteins were proved to involve in modulation ERɑ signalling, such as RNF31, RBCK1, BRCA1 and RNF8 . Some of them may modulate ERɑ protein stability via certain ubiquitination manner, such as RNF31 and RNF8 .…”

“…Interestingly, quite a few RING finger proteins were proved to involve in modulation ERɑ signalling, such as RNF31, RBCK1, BRCA1 and RNF8 . Some of them may modulate ERɑ protein stability via certain ubiquitination manner, such as RNF31 and RNF8 . The others may control ERɑ transcription level, For example, RBCK1 recruitment to ERɑ promoter regions is required for ERɑ gene expression and breast cancer cell proliferation …”