Anovel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system. Co-activators and co-repressors in the integration of transcriptional responses. 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.
Several DRIP/ARC subunits are also components of other potentially related cofactors, such as CRSP 6, NAT 7, SMCC 8 and the mouse Mediator 9, indicating that unique classes of activators may share common sets or subsets of cofactors. 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. 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. 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. 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. 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. Nuclear receptors modulate the transcription of genes in direct response to small lipophilic ligands.