title: Transcriptional activities of retinoic acid receptors.
abstract: Vitamin A derivatives plays a crucial role in embryonic development, as demonstrated by the teratogenic effect of either an excess or a deficiency in vitamin A. Retinoid effects extend however beyond embryonic development, and tissue homeostasis, lipid metabolism, cellular differentiation and proliferation are in part controlled through the retinoid signaling pathway. Retinoids are also therapeutically effective in the treatment of skin diseases (acne, psoriasis and photoaging) and of some cancers. Most of these effects are the consequences of retinoic acid receptors activation, which triggers transcriptional events leading either to transcriptional activation or repression of retinoid-controlled genes. Synthetic molecules are able to mimic part of the biological effects of the natural retinoic acid receptors, all-trans retinoic acid. Therefore, retinoic acid receptors are considered as highly valuable therapeutic targets and limiting unwanted secondary effects due to retinoid treatment requires a molecular knowledge of retinoic acid receptors biology. In this review, we will examine experimental evidence which provide a molecular basis for the pleiotropic effects of retinoids, and emphasize the crucial roles of coregulators of retinoic acid receptors, providing a conceptual framework to identify novel therapeutic targets.
authors.affiliation: INSERM U459 and Ligue Nationale Contre le Cancer, Faculté de Médecine de Lille, 59045 Lille cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Perrine J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Sébastien
authors.initials: S
authors.lastname: Flajollet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dedieu
authors.forename: Xavier
authors.initials: X
authors.lastname: Billaut
authors.forename: Bruno
authors.initials: B
authors.lastname: Lefebvre
mesh_terms: D000818:Animals; D000013:Congenital Abnormalities; D005786:Gene Expression Regulation; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000502:physiology*; D012176:Retinoids / Q000494:pharmacology / Q000502:physiology; D012177:Retinol-Binding Proteins / Q000502:physiology; D018808:Transcription Factor AP-1; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014802:Vitamin A Deficiency
chemical_list: D018168:Receptors, Retinoic Acid; D012176:Retinoids; D012177:Retinol-Binding Proteins; D018808:Transcription Factor AP-1