Signal transduction by retinoid receptors. 1993

M Pfahl
Cancer Center, La Jolla Cancer Research Foundation, Calif.

Vitamin A derivatives (retinoids) affect a large variety of fundamental biological processes. Understanding of the signaling mechanism has been greatly advanced by the cloning of specific retinoid receptors. These regulatory proteins belong to the steroid/thyroid hormone nuclear receptor superfamily. Two types of retinoid receptors have been identified, the retinoic acid receptors (RAR alpha, beta and gamma) and the retinoid X receptors (RXR alpha, beta, and gamma). Similar to the steroid hormone receptors, the retinoid receptors bind to specific DNA sequences that have diad symmetries. However, the RARs require heterodimerization with RXRs for efficient DNA binding and gene regulation, while the RXRs can bind to DNA and function as homodimers in the presence of 9-cis-retinoic acid. In addition, RXRs can form heterodimers with thyroid hormone receptors and the vitamin D3 receptor and other receptors. Thus the RXRs have a very central role in serving as a partner for several hormone and vitamin receptors and thus may allow cross talk between different hormone signals. Retinoid responses can be restricted by the COUP-TF orphan receptors which bind to overlapping DNA sequences. Besides the classical way of action via DNA binding, the retinoid receptors can also interfere with other signaling pathways by interacting with the transcription factor AP-1. The advances made in understanding the mechanism of action of retinoids promise to contribute to the understanding and control of physiological responses and diseases.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012176 Retinoids A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization. Retinoid
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D018168 Receptors, Retinoic Acid Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized. Retinoic Acid Receptors,Retinoic Acid-Binding Proteins,Retinoic Acid Receptor,Proteins, Retinoic Acid-Binding,Receptor, Retinoic Acid,Retinoic Acid Binding Proteins

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