International Union of Pharmacology. LX. Retinoic Acid Receptors

Abstract

Abstract--Retinoid is a term for compounds that bind to and activate retinoic acid receptors (RAR␣, RAR␤, and RAR␥), members of the nuclear hormone receptor superfamily. The most important endogenous retinoid is all-trans-retinoic acid. Retinoids regulate a wide variety of essential biological processes, such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation and apoptosis, and homeostasis, as well as their disorders. This review summarizes the considerable amount of knowledge generated on these receptors.

Retinoic Acid Receptor β Stimulates Hepatic Induction of Fibroblast Growth Factor 21 to Promote Fatty Acid Oxidation and Control Whole-body Energy Homeostasis in Mice

“…The calculated energy expenditure was also increased. Due possibly to the increase in both VO 2 and VCO 2 , the respiratory quotient (RQ ϭ VCO 2 /VO 2 ) appeared unchanged in mice expressing RAR␤, compared with control mice in fed and fasted states (data not shown). The RQ was not affected in mice expressing RAR␤, which possibly reflects the relatively equal use of carbohydrates versus lipids as a source of energy in whole body, as was described previously (45).…”

“…RA is currently used for clinical cancer therapy (1). RAR is the ligand-dependent nuclear receptor that heterodimerizes with the retinoid X receptor (RXR) to transactivate its target genes by binding to gene promoters harboring retinoic acid response elements (RAREs) (1,2). RAR␤ is relatively more abundant in the liver compared with RAR␣ and RAR␥ (3).…”

“…All-trans-retinoic acid (RA), 3 a major active metabolite of vitamin A, plays essential roles in development, cellular differentiation, and survival through three retinoic acid receptors (RARs) of the nuclear receptor superfamily (1,2). RA is currently used for clinical cancer therapy (1).…”

Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression

“…In most cell proliferation/differentiation models, all-trans retinoic acid (atRA) is known primarily as a differentiation agent acting through the RAR family (21,22) Activation of these receptors by atRA normally leads to stem cell differentiation (23)(24)(25). However, atRA has also been known to exert some nongenomic actions to affect several cellular processes, and involves, mostly, activation of extracellular signal-regulated kinase (ERK) (26)(27)(28)(29).…”

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

“…The vitamin A metabolite retinoic acid (RA) 3 regulates gene transcription by activating several members of the nuclear receptor family of transcription factors: the classical RA receptors (RARs) (1,2) and peroxisome proliferator-activated receptor ␤/␦ (PPAR␤/␦) (3,4). The partitioning of RA between these receptors is regulated by two intracellular lipid-binding proteins: cellular retinoic acid-binding protein 2 (CRABP2), which has a high affinity for the hormone and shuttles it to RARs, and fatty acid-binding protein 5 (FABP5), which has a lower affinity for RA and delivers it to PPAR␤/␦.…”