Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth
| Autor: | Grace Hsieh, John H. Youson, Ralph M. Bernstein, G. Kerr Whitfield, Hope Dang, Lori A. Manzon, John J. Marchalonis, Tara Francis Bunag, Samuel F. Schluter, Mark R. Haussler, Carlos Encinas Dominguez |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Molecular Sequence Data Gene Expression Receptors Cytoplasmic and Nuclear Calcitriol receptor Intestinal absorption Evolution Molecular Endocrinology Calcification Physiologic Calcitriol Cytochrome P-450 Enzyme System Hair cycle Internal medicine Gene expression medicine Animals Humans Amino Acid Sequence Cloning Molecular Phylogeny Reporter gene biology Base Sequence Lamprey Age Factors Lampreys biology.organism_classification Protein Structure Tertiary Petromyzon Cartilage Vertebrates Osteocalcin biology.protein Receptors Calcitriol Tooth |
| Zdroj: | Endocrinology. 144(6) |
| ISSN: | 0013-7227 |
| Popis: | The nuclear vitamin D receptor (VDR) mediates the actions of its 1,25-dihydroxyvitamin D(3) ligand to control gene expression in terrestrial vertebrates. Prominent functions of VDR-regulated genes are to promote intestinal absorption of calcium and phosphate for bone mineralization and to potentiate the hair cycle in mammals. We report the cloning of VDR from Petromyzon marinus, an unexpected finding because lampreys lack mineralized tissues and hair. Lamprey VDR (lampVDR) clones were obtained via RT-PCR from larval protospleen tissue and skin and mouth of juveniles. LampVDR expressed in transfected mammalian COS-7 cells bound 1,25-dihydroxyvitamin D(3) with high affinity, and transactivated a reporter gene linked to a vitamin D-responsive element from the human CYP3A4 gene, which encodes a P450 enzyme involved in xenobiotic detoxification. In tests with other vitamin D responsive elements, such as that from the rat osteocalcin gene, lampVDR showed little or no activity. Phylogenetic comparisons with nuclear receptors from other vertebrates revealed that lampVDR is a basal member of the VDR grouping, also closely related to the pregnane X receptors and constitutive androstane receptors. We propose that, in this evolutionarily ancient vertebrate, VDR may function in part, like pregnane X receptors and constitutive androstane receptors, to induce P450 enzymes for xenobiotic detoxification. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|