Cavaillès V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner P J, Parker M G
Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London, UK.
EMBO J. 1995 Aug 1;14(15):3741-51. doi: 10.1002/j.1460-2075.1995.tb00044.x.
A conserved region in the hormone-dependent activation domain AF2 of nuclear receptors plays an important role in transcriptional activation. We have characterized a novel nuclear protein, RIP140, that specifically interacts in vitro with this domain of the estrogen receptor. This interaction was increased by estrogen, but not by anti-estrogens and the in vitro binding capacity of mutant receptors correlates with their ability to stimulate transcription. RIP140 also interacts with estrogen receptor in intact cells and modulates its transcriptional activity in the presence of estrogen, but not the anti-estrogen 4-hydroxytamoxifen. In view of its widespread expression in mammalian cells, RIP140 may interact with other members of the superfamily of nuclear receptors and thereby act as a potential co-activator of hormone-regulated gene transcription.
核受体激素依赖性激活结构域AF2中的一个保守区域在转录激活中起重要作用。我们鉴定了一种新型核蛋白RIP140，它在体外与雌激素受体的这一结构域特异性相互作用。雌激素可增强这种相互作用，但抗雌激素则不能，并且突变受体的体外结合能力与其刺激转录的能力相关。RIP140在完整细胞中也与雌激素受体相互作用，并在有雌激素存在时调节其转录活性，但在抗雌激素4-羟基他莫昔芬存在时则不然。鉴于其在哺乳动物细胞中的广泛表达，RIP140可能与核受体超家族的其他成员相互作用，从而作为激素调节基因转录的潜在共激活因子发挥作用。
