Transcriptional activities of retinoic acid receptors.
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.
Lefebvre
Philippe
P
INSERM U459 and Ligue Nationale Contre le Cancer, Faculté de Médecine de Lille, 59045 Lille cedex, France.
Martin
Perrine J
PJ
Flajollet
Sébastien
S
Dedieu
Stéphane
S
Billaut
Xavier
X
Lefebvre
Bruno
B
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
D018168:Receptors, Retinoic Acid; D012176:Retinoids; D012177:Retinol-Binding Proteins; D018808:Transcription Factor AP-1