Halachmi S, Marden E, Martin G, MacKay H, Abbondanza C, Brown M
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA.
Science. 1994 Jun 3;264(5164):1455-8. doi: 10.1126/science.8197458.
The estrogen receptor is a transcription factor which, when bound to estradiol, binds DNA and regulates expression of estrogen-responsive genes. A 160-kilodalton estrogen receptor-associated protein, ERAP160, was identified that exhibits estradiol-dependent binding to the receptor. Mutational analysis of the receptor shows that its ability to activate transcription parallels its ability to bind ERAP160. Antiestrogens are unable to promote ERAP160 binding and can block the estrogen-dependent interaction of the receptor and ERAP160 in a dose-dependent manner. This evidence suggests that ERAP160 may mediate estradiol-dependent transcriptional activation by the estrogen receptor. Furthermore, the ability of antiestrogens to block estrogen receptor-ERAP160 complex formation could account for their therapeutic effects in breast cancer.
雌激素受体是一种转录因子，当与雌二醇结合时，它会结合DNA并调节雌激素反应性基因的表达。一种160千道尔顿的雌激素受体相关蛋白ERAP160被鉴定出来，它表现出对受体的雌二醇依赖性结合。对该受体的突变分析表明，其激活转录的能力与其结合ERAP160的能力平行。抗雌激素不能促进ERAP160的结合，并且可以剂量依赖性地阻断受体与ERAP160的雌激素依赖性相互作用。这一证据表明，ERAP160可能介导雌激素受体的雌二醇依赖性转录激活。此外，抗雌激素阻断雌激素受体-ERAP160复合物形成的能力可以解释它们在乳腺癌中的治疗作用。
