Glucocorticoid Receptor-Interacting Protein-1 and Receptor-Associated Coactivator-3 Differentially Interact with the Vitamin D Receptor (VDR) and Regulate VDR-Retinoid X Receptor Transcriptional Cross-Talk*
| Autor: | Janelle B. Barry, Laura L. Issa, Robert L. Sutherland, Gary M. Leong, John A. Eisman |
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| Rok vydání: | 2001 |
| Předmět: |
Electrophoresis
musculoskeletal diseases medicine.medical_specialty Receptors Retinoic Acid Blotting Western Osteocalcin Saccharomyces cerevisiae Retinoid X receptor Biology Transfection Calcitriol receptor Cell Line Nuclear Receptor Coactivator 3 Nuclear Receptor Coactivator 2 Endocrinology Internal medicine Coactivator polycyclic compounds medicine Animals Promoter Regions Genetic Receptor digestive oral and skin physiology DNA Receptor Cross-Talk Blotting Northern Precipitin Tests Retinoid X Receptors Nuclear receptor Vitamin D3 Receptor Nuclear receptor coactivator 3 Trans-Activators Cancer research Nuclear receptor coactivator 2 Receptors Calcitriol lipids (amino acids peptides and proteins) Transcription Factors |
| Zdroj: | Endocrinology. 142:1606-1615 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | The vitamin D(3) receptor (VDR) is a ubiquitously expressed nuclear hormone receptor, and its ligand, calcitriol, has diverse biological effects. The extent to which transcriptional coactivators are involved in modulating tissue-specific functions of the VDR is unclear. Hence, the current studies investigated the role of p160 coactivators in regulating VDR function and interaction with RXR. Two p160 coactivators, glucocorticoid receptor-interacting protein-1 (GRIP1) and receptor-associated coactivator-3 (RAC3), which are expressed in an inverse fashion in cell lines representative of calcitriol target tissues, interacted directly with the VDR, both in vitro and in yeast cells, but only in the presence of calcitriol. Deletional analyses of VDR indicated that GRIP1 and RAC3 required an intact VDR activation function (AF-2) domain for efficient interaction as well as additional but distinct regions of the VDR. Coexpression experiments in yeast cells indicated that both GRIP1 and RAC3 coassemble with the VDR to form an active transcriptional complex. They also form ternary complexes with VDR homodimers and VDR:RXRalpha heterodimers. In mammalian cells, GRIP1 augmented VDR activation of the osteocalcin promoter, whereas RAC3 enhanced VDR activation indirectly through RXR. These data suggest different coactivators regulate VDR function via distinct mechanisms and support the hypothesis that the VDR recruits different coactivators depending on specific gene and cellular contexts. |
| Databáze: | OpenAIRE |
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