An E3 ligase that regulates expression of ESR1 and a co-factor of ESR1 in breast cancer cells.

We discovered regulation of ESR1 and GREB1 in breast cancer cells by the E3 ligase RNF168. RNF168 has functions related to DNA damage signaling interacting with H2AX and ubiquitination of the DNA. and is a K27 ubiquitin chain-specific ligase. We demonstrate here that RNF168 expression is a correlate or strong predictor of tumor size in humans with cancer. RNF168 expression was a significant component of the gene signature of the Xist-expressing human embryonic stem cell in humans whose genomes contained an XX (females). Together we describe a relationship between the E3 ligase RNF168 and estrogen steroid hormone signaling which is likely shaped by interactions with Xist at least in part in relation to a recently described requirement for the Xist ncRNA in DNA damage marked by H2AX, a feature which positively associated with tumor size in humans.