Retinobenzoic acids and nuclear retinoic acid receptors

Abstract

Retinoids (retinoic acid and its analogs) are widely involved in the control of cell proliferation, cell differentiation and embryonic development. A series of potent and novel synthetic retinoids named retinobenzoic acids has been developed. Retinobenzoic acids have proven to be useful tools in the investigation of the molecular mechanisms of retinoidal actions. Retinoids elicit their biological effects by binding to and activating specific nuclear receptors for retinoids (RAR's) which belong to the steroid/thyroid nuclear receptor superfamily. Recent investigations concerning the structure and function of nuclear receptors, namely of RAR's, are reviewed. Three subtypes of RAR (RAR-alpha, RAR-beta and RAR-gamma) have been identified so far. Each RAR is considered to play particular roles in the retinoidal actions. The role of each RAR is discussed in relation to their features and to the structure-activity relationships of retinoids. RAR's act as retinoid-dependent transcription factors which bind to a specific site of the gene and control its expression. Recent progress in the investigation of the interaction of RAR's with the responsive genes and with nuclear co-factors is reviewed. The diversity of retinoidal actions are possibly explained by the diversity of RAR's in their structure and in their spatial and temporal distribution, by the diversity of base sequences which interact with RAR's, by the diversity of cell type-specifically determined hierarchy of gene expression, and by the diversity of the nuclear factors which interact with RAR's.