Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex
Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex
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DOI：
10.1038/19783
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发表时间：
1999-04-29
期刊：
影响因子：
64.8
通讯作者：
Freedman, LP
中科院分区：
文献类型：
--
作者：
Rachez, C;Lemon, BD;Freedman, LP
核受体直接响应于小的亲脂性配体来调节基因的转录。与配体的结合诱导核受体的构象变化，使受体能够与几种类型的辅因子相互作用，这些辅因子对转录激活（反式激活）至关重要（1）。我们之前描述了一组独特的配体依赖性蛋白质，称为DRIP，与维生素D受体（VDR）相互作用;这些蛋白质共同构成了一种新的辅因子复合物（2）。DRIP与几种核受体结合，并在无细胞转录试验中介导VDR和甲状腺激素受体的配体依赖性转录增强（2，3）。在这里，我们报告了13个DRIP的身份，构成这个复杂的，并表明该复合物有一个核心功能，在染色质模板上的VDR依赖的转录激活。DRIP与另一种称为ARC的新辅因子复合物的组分几乎无法区分，ARC被其他类型的转录激活因子招募，以介导染色质组装模板上的反式激活（4，5）。几种DRIP/ARC亚基也是其他潜在相关辅因子的组分，如CRSP6、NAT（7）、SMCC 8和小鼠介体（9），表明独特类别的激活剂可能共享共同的辅因子集合或子集。核受体配体的作用可能部分是将这种辅因子复合物募集到受体上，并在这样做的过程中增强靶基因的转录。
Nuclear receptors modulate the transcription of genes in direct response to small, lipophilic ligands. Binding to ligands induces conformational changes in the nuclear receptors that enable the receptors to interact with several types of cofactor that are critical for transcription activation (transactivation)(1). We previously described a distinct set of ligand-dependent proteins called DRIPs, which interact with the vitamin D receptor (VDR); together, these proteins constitute a new cofactor complex(2). DRIPs bind to several nuclear receptors and mediate ligand-dependent enhancement of transcription by VDR and the thyroid-hormone receptor in cell-free transcription assays(2,3). Here we report the identities of thirteen DRIPs that constitute this complex, and show that the complex has a central function in hormone-dependent transactivation by VDR on chromatin templates. The DRIPs are almost indistinguishable from components of another new cofactor complex called ARC, which is recruited by other types of transcription activators to mediate transactivation on chromatin-assembled templates(4,5). Several DRIP/ARC subunits are also components of other potentially related cofactors, such as CRSP6, NAT(7), SMCC8 and the mouse Mediator(9), indicating that unique classes of activators may share common sets or subsets of cofactors. The role of nuclear-receptor ligands may, in part, be to recruit such a cofactor complex to the receptor and, in doing so, to enhance transcription of target genes.