XBP-1和ERα存在相互作用

XBP-1 Interacts with Estrogen Receptor α(ERα)

雌激素受体α(ERα)是乳腺癌治疗的靶标和预后的指标。在乳腺癌中 ,人X盒结合蛋白 1(XBP_1)与ERα共表达 ,并在一些乳腺肿瘤中过表达。这些结果提示 ,XBP_1与ERα可能存在相互作用。XBP_1由于剪切方式不同 ,产生两种形式的XBP_1,即XBP_1S和XBP_1U。体外GST沉淀实验表明 ,XBP_1S和XBP_1U均能结合ERα ,XBP_1S的结合能力大于XBP_1U。体内免疫共沉淀实验也表明 ,XBP_1S和XBP_1U以激素不依赖的方式与ERα结合。ERα通过其DNA结合结构域与XBP_1S和XBP_1U结合 ,而XBP_1S和XBP_1U通过其N末端的亮氨酸拉链结构域和C末端的转录激活结构域与ERα相互作用。这些结果提示 ,XBP_1S和XBP_1U可能通过与ERα的相互作用参与雌激素受体信号途径。

Estrogen receptor α (ERα) has been a primary target of treatment as well as a prognostic indicator for breast cancer. The level of human X-box binding protein 1 (XBP-1) mRNA was related with that of ERα in breast tumors and was over-expressed in some breast tumors. These previous studies suggested that XBP-1 may interact with ERα. XBP-1 has two isoforms, XBP-1S and XBP-1U, as the result of unique splicing. GST pull-down assay showed that both XBP-1S and XBP-1U bound to ERα in vitro. The binding of XBP-1S to ERα was stronger than that of XBP-1U to ERα. Co-immunoprecipitation revealed that the binding was in a ligand-independent manner. XBP-1S and XBP-1U interacted with the region of ERα that contains a DNA-binding domain. The ERα-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, the N-terminal basic region leucine zipper domain (bzip) and the C-terminal activation domain. These findings suggest that XBP-1S and XBP-1U may participate in ERα signaling pathway through the mediation of ERα.