The molecular physiology of nuclear retinoic acid receptors. From health to disease.
The nuclear retinoic acid (RA) receptors (RARα, β and γ) are transcriptional transregulators, which control the expression of specific gene subsets subsequently to ligand binding and to strictly controlled phosphorylation processes. Consequently RARs maintain homeostasis through the control of cell proliferation and differentiation. Today, it is admitted that, analogous to the paradigm established by the hematopoietic system, most adult tissues depict a differentiation hierarchy starting from rare stem cells. Here we highlight that the integrity of RARs is absolutely required for homeostasis in adults. Indeed, strictly controlled levels of RARs are necessary for the correct balance between self-renewal and differentiation of tissue stem cells. In addition, loss, accumulation, mutations or aberrant modifications of a specific RAR lead to uncontrolled proliferation and/or to differentiation block and thereby to cancer. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM, U596, CNRS, UMR7104, Université de Strasbourg, 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France.
Vanessa
V
Duong
Cécile
C
Rochette-Egly
D000818:Animals; D002493:Central Nervous System Diseases / Q000503:physiopathology; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000503:physiopathology; D010766:Phosphorylation; D011487:Protein Conformation; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D012871:Skin Diseases / Q000503:physiopathology; D014158:Transcription, Genetic
D018168:Receptors, Retinoic Acid