TOR: a new orphan receptor expressed in the thymus that can modulate retinoid and thyroid hormone signals
| Autor: | Maria A. Ortiz, Magnus Pfahl, F J Piedrafita, Robert G. Maki |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Receptors
Retinoic Acid T-Lymphocytes Molecular Sequence Data Gene Expression Sequence Homology Tretinoin Thymus Gland Biology Cell Line Thyroid hormone receptor beta Mice Endocrinology Animals Amino Acid Sequence Cloning Molecular Molecular Biology Repetitive Sequences Nucleic Acid Orphan receptor Binding Sites Receptors Thyroid Hormone Thyroid hormone receptor Base Sequence Retinoid X receptor alpha 3T3 Cells DNA General Medicine Nuclear Receptor Subfamily 1 Group F Member 3 Retinoid X receptor gamma Cell biology Retinoid X Receptors Nuclear receptor Biochemistry Thyroid hormone receptor alpha Triiodothyronine Retinoid X receptor beta Transcription Factors |
| Zdroj: | Molecular Endocrinology. 9:1679-1691 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/mend.9.12.8614404 |
| Popis: | Vitamin A and other fat-soluble hormones and vitamins have important roles as modulators of essential biological processes such as homeostasis, development, differentiation, and oncogenesis and also as regulators of the immune system. The active form of vitamin A, retinoic acid, as well as vitamin D3 and thyroid hormones exert their actions by binding to specific nuclear receptors that represent one subfamily of the steroid/thyroid hormone receptor superfamily. To identify new members of the retinoid/thyroid hormone receptor subfamily that could play a role in the immune system, a screening of a T cell cDNA library was performed using a retinoid X receptor probe. A clone was isolated encoding a novel nuclear receptor expressed mainly in the thymus and T cell lines. This new receptor, TOR (thymus orphan receptor), is most closely related in both its DNA-binding domain and ligand-binding domain, 90% and 53%, respectively, to ROR alpha/RZR alpha and clusters with these two receptors and RZR beta in a phylogenetic tree, when both the DNA-binding domain and the ligand-binding domain sequences of nuclear receptors are compared. Thus, TOR is part of a subgroup of receptors, one of which has recently been reported to be activated by melatonin. TOR binds specifically to a direct repeat of the half-site sequence 5'-AGGTCA-3' with a four- or five-nucleotide spacer, DNA sequences that also serve as binding sites for thyroid hormone (TR), and retinoic acid receptors (RAR). In transient transfection experiments TOR does not activate a reporter gene carrying these sequences in the absence or the presence of any known nuclear receptor ligands. TOR, however, is able to repress TR and RAR activity on DR-4-TREs or DR-5-RAREs, respectively. Therefore, our data suggest that TOR, similar to COUP-TF, can negatively regulate retinoic acid and thyroid hormone signals. However, the response elements recognized by TOR and COUP-TF differ as do the expression patterns of these receptors. Thus, one important role of TOR could be to modulate retinoid and thyroid hormone signals in the thymus. |
| Databáze: | OpenAIRE |
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