Thomas H E, Stunnenberg H G, Stewart A F
Gene Expression Programme, EMBL, Heidelberg, Germany.
Nature. 1993 Apr 1;362(6419):471-5. doi: 10.1038/362471a0.
Ecdysone in Drosophila has been a paradigm for steroid hormones since its ability to induce gene activity directly was demonstrated by its effects on moulting and polytene chromosome puffing. The ecdysone receptor (EcR) was recently confirmed as a member of the nuclear receptor superfamily by cloning and characterization in a Drosophila cell line. Here we show that EcR needs to heterodimerize with either the retinoid X receptor (RXR) or its Drosophila homologue, ultraspiracle (USP), for DNA binding and transactivation. These results place the ecdysone receptor in the heterodimerizing class of the nuclear receptor superfamily and demonstrate that the role of RXR/USP as a central and promiscuous partner in mediating the activity of these receptors is highly conserved. Whereas EcR-USP DNA-binding activity is unaffected by hormone, EcR-RXR DNA-binding activity is stimulated by either ecdysteroid or 9-cis-retinoic acid, demonstrating that hormone can play a role in heterodimer stabilization.
自从蜕皮激素对果蝇蜕皮和多线染色体胀泡的影响证明其具有直接诱导基因活性的能力以来，它一直是类固醇激素的范例。最近，通过在果蝇细胞系中的克隆和表征，蜕皮激素受体（EcR）被确认为核受体超家族的成员。我们在此表明，EcR需要与视黄酸X受体（RXR）或其果蝇同源物超气门蛋白（USP）异源二聚化，才能进行DNA结合和反式激活。这些结果将蜕皮激素受体置于核受体超家族的异源二聚化类别中，并证明RXR/USP作为介导这些受体活性的核心且通用的伴侣的作用是高度保守的。虽然EcR-USP的DNA结合活性不受激素影响，但EcR-RXR的DNA结合活性受到蜕皮甾类或9-顺式视黄酸的刺激，表明激素可在异源二聚体稳定中发挥作用。
