Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity
Article Abstract:
Thyroid hormone and retinoic acid (vitamin A acid) play integral roles in growth and development. They act as signals which trigger specific steps in biochemical mechanisms. The interaction and analogous capabilities of these two compounds were investigated by examining the behavior of clones of nuclear receptors for both retinoic acid and thyroid hormone. (Receptors are areas of a cell that bind selectively with a specific substance.) The two nuclear receptors, thyroid-receptor and retinoic acid receptor, showed similar DNA-binding structure (homology) and were found to act through the same DNA sequence. Two types of retinoic acid receptors can control transcription (a step in the replication of genetic material) for two distinct thyroid-hormone responsive elements. The thyroid-hormone receptor may have more than one role in the regulation of various mechanisms. When the thyroid-hormone receptors are exposed to thyroid hormone they act as specific transcriptional activators. When no hormone is present, they act as repressors. This finding may be significant if it is found to be characteristic of other nuclear receptors. The dual role for thyroid-hormone receptors as both an activator and repressor of retinoic-acid activity is indicated. The mechanism shows that it is possible for some nuclear receptors to have a dual regulatory role, acting as receptors and repressors. This highly selective behavior indicates an increased specificity of gene regulation. A new level of regulation by negative control is implied, its function being dependent upon the absence, as well as the presence, of other compounds.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1989
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Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid
Article Abstract:
Nine-cis-retinoic acid, a natural vitamin A derivative, stimulates development of retinoid X receptor (RXR) homodimers which then attach to the palindromic thyroid hormone response element. This process shows that retinoids are able to carry out their functions when ligand-created homodimers control separate retinoid response pathways. Moreover, RXR and retinoic acid receptors influence distinct response pathways. RXR homodimers also stimulate the ApoAI-retinoic acid response element.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1992
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A transcriptional co-repressor that interacts with nuclear hormone receptors
Article Abstract:
SMRT, a receptor-interacting protein, is a new co-repressor which regulates the transcriptional silencing of the thyroid-hormone receptor and retinoic-acid receptor. Ligand dissociates the interaction of SMRT with receptors, when attached to DNA-response elements or in solution. SMRT is a potential tool for establishing the molecular basis of nuclear hormone receptors trans-repression.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1995
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