Retinoic acid signaling pathways

Leid, M., Kastner, R, and Chambon, P., Multiplicity generates diversity in the retinoic acid signalling pathways, Trends. Biochem. Sci., 17, 427, 1992. 

The adverse effects of ethanol are not limited to the metabolism of ethanol itself. Vitamin A (retinol) is converted into retinoic acid, an important signal molecule for growth and development in vertebrates, by the same dehydrogenases that metabolize ethanol. Consequently, this activation does not take place in the presence of ethanol, which acts as a competitive inhibitor. Moreover, the MEOS system induced by ethanol inactivates retinoic acid. These disruptions in the retinoic acid signaling pathway are believed to be responsible, at least in part, for fetal alcohol syndrome as well as the development of a variety of cancers. 

Murphy KA, Quadro L, White LA (2007) The intersection between the aryl hydrocarbon receptor (AhR)- and retinoic acid-signaling pathways. Vitam Horm 75 33-67 Nebert DW, Dalton TP, Okey AB, Gonzalez FJ (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYPl enzymes in environmental toxicity and cancer. J Biol Chem... 

Escriva, H., N. D. Holland, H. Gronemeyer, C. Laudet, and L. Z. Holland. 2002. The Retinoic Acid Signaling Pathway Regulates Anterior/Posterior Patterning in the Nerve Cord and Pharynx of Amphioxus, a Chordate Lacking Neural Crest. Development 129, no 12 2905-16. 

Mark, M., N. B. Ghyselinck, and P. Chambon. 2006. Function of Retinoid Nuclear Receptors. Lessons from Genetic and Pharmacological Dissections of the Retinoic Acid Signaling Pathway During Mouse Emhryogenesis. Annu Rev Pharmacol 46 451-80. 

Muller, W. E. G., M. Binder, J. von Lindg, et al. 2011. Interaction of the Retinoic Acid Signaling Pathway with Spicule Formation in the Marine Sponge Suberites domuncida Through Activation of Bone Morphogenetie Protein-1. Biochem BiophysActa 1810, no 12 1178-94. 

Theodosiou, M., V. Laudet, and M. Schubert. 2010. From Carrot to Clinic An Overview of the Retinoic Acid Signaling Pathway. Cell Mol Life Sci Cl, no 9 1423-45. 

Theodosiou M, Laudet V, Schubert M. 2010. From carrot to clinic An overview of the retinoic acid signaling pathway. Cell Mol Life Sci. 67 1423-1445. 

Mangelsdorf DJ, Evans RM (1995) The RXR heterodimers and orphan receptors. Cell 83 841-850 Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P et al (1995) The nuclear receptor superfamily—the 2nd decade. Cell 83 835-839 Leid M, Kastner P, Chambon P (1992) Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci 17 427-433... 

Nugent, P. and Greene, R. M (1994) Interactions between the TGF-P and retinoic acid signal transduction pathways in embryonic palatal cells. Differentiation 58, 149-155... 

There are several alternative pathways associated with the balance between proliferation and apoptosis that are affected by lycopene treatment, especially the insulin-like growth factor (IGF) signaling pathway. Another is the possibility that lycopene or one of its breakdown products has retinoid activity. Kotake-Nara et al. compared acyclo-retinoic acid, an in vitro oxidation product of lycopene, to four actively researched anticarcinogenic retinoids. Acycloretinoic acid was found to more actively reduce PC-3 and DU-145 cell viabilities (but not LNCaP) through apoptosis in a medium already containing small amounts of natural retinoids. But study concentrations were 20 pM, far above physiologically relevant lycopene concentrations, let alone the smaller concentration of one of its breakdown products. Acycloretinoic acid had a very low affinity for the retinoid X receptors (RXR) and retinoic acid receptors (RAR) receptors (Kotake-Nara et al. 2002). 

Elias KM, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, O Shea JJ Retinoic acid inhibits Thl7 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 2008 111 1013-1020. 

Lipophilic signaling substances include the steroid hormones, calcitriol, the iodothy-ronines (T3 and T4), and retinoic acid. These hormones mainly act in the nucleus of the target cells, where they regulate gene transcription in collaboration with their receptors and with the support of additional proteins (known as coactivators and mediators see p.244). There are several effects of steroid hormones that are not mediated by transcription control. These alternative pathways for steroid effects have not yet been fully explained. 

Impairment of the retinoid signal transduction pathways occurs as a result of prolonged UV exposure. Down regulation of nuclear receptors for Vitamin A occurs,269 resulting in a functional deficiency of Vitamin A. Application of Vitamin A derivatives would appear to be an obvious treatment modality. Topical application of Vitamin A does increase the HA in the epidermal layer, increasing the thickness of the HA meshwork after prolonged treatment.270 Vitamin A thus enhances repair, as can be demonstrated in photo-aged hairless mouse model.271 The decline in GAG, and in particular HA deposition that occurs with UVB irradiation, can be entirely prevented by retinoic acid treatment. 

Schrader, M., Bendik, J., Becker-Andre, M., and Carlberg, C., Interaction between retinoic acid and retinoic acid and vitamin D signalling pathways. J. Biol. Chem. 268, 17830-17836 (1993). 

The vitamin D receptor- RXR heterodimer binds in 5 RXR-VDR3 polarity to a direct repeat hormone response element However, the vitamin D receptor also forms heterodimers with the retinoic acid receptor and the thyroid hormone receptor. All three vitamin D receptor dimers can interact with either direct repeat or inverted palindromic hormone response elements. In heterodimers, the vitamin D receptor may be at the 5 -position or 3 -position, resulting in six types of activated vitamin D receptor dimers that can bind to two types of response elements, raising the possibility of multiple signaling pathways (Carlberg, 1996 Carlberg et al., 2001 Yamada et al., 2001b). 

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