The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ER and enhances ER target gene expression in breast cancer cells

Abstract

Estrogen/ER signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ER to potentiate ER target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ER, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ER transcriptional activity and concomitantly enhances ER acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ER responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ER and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer.