Zhang H, Thomsen J S, Johansson L, Gustafsson J A, Treuter E
Department of Biosciences at Novum, Karolinska Institute, S-14157 Huddinge, Sweden.
J Biol Chem. 2000 Dec 22;275(51):39855-9. doi: 10.1074/jbc.C000567200.
We have discovered that the orphan receptor DAX-1 (NROB1) interacts with the estrogen receptors ERalpha and ERbeta. Interaction occurs with ligand-activated ERs in solution and on DNA and is mediated by the unique DAX-1 N-terminal repeat domain. Each of the three repeats contains a leucine-rich receptor-binding motif, known as the LXXLL motif, which is usually found in nuclear receptor coactivators. We have demonstrated that DAX-1 functions as an inhibitor of ER activation in mammalian cells and suggest a mechanism involving two sequential events, occupation of the ligand-induced coactivator-binding surface and subsequent recruitment of corepressors. Accordingly, we propose that DAX-1 itself acts as a corepressor for ERs. Because DAX-1 is coexpressed with ERs in reproductive tissues, these interactions could play significant roles by influencing estrogen signaling pathways. Our results point at functional similarities between DAX-1 and the orphan receptor SHP (NROB2) in that they have acquired features of transcriptional coregulators that are unique for members of the nuclear receptor family.
我们发现孤儿受体DAX-1（NROB1）可与雌激素受体ERα和ERβ相互作用。这种相互作用发生在溶液中和DNA上的配体激活型ERs之间，由独特的DAX-1 N端重复结构域介导。三个重复序列中的每一个都包含一个富含亮氨酸的受体结合基序，即LXXLL基序，该基序通常存在于核受体共激活因子中。我们已经证明，DAX-1在哺乳动物细胞中作为ER激活的抑制剂发挥作用，并提出了一种涉及两个连续事件的机制，即占据配体诱导的共激活因子结合表面以及随后募集共抑制因子。因此，我们认为DAX-1本身作为ERs的共抑制因子发挥作用。由于DAX-1与ERs在生殖组织中共表达，这些相互作用可能通过影响雌激素信号通路发挥重要作用。我们的结果表明DAX-1与孤儿受体SHP（NROB2）在功能上具有相似性，即它们获得了核受体家族成员特有的转录共调节因子特征。
