ABSTRACT

Various attempts designed to determine the molecular mechanism of retinoid actions in the control of epithelial differentiation, growth, and tumorigenesis have centered on intracellular retinoid-binding proteins. It was suggested that this action of retinol and retinoic acid (RA) may be mediated by their well-known cellular binding proteins, cellular retinol-binding protein and cellular retinoic acid-binding protein (CRABP), respectively. These proteins have been detected in a variety of cells and tissues. The role of CRABP in mediating the biological effects of RA in the control of epithelial differentiation was further confirmed by the existence of a correlation between the binding affinities of various synthetic analogs of RA to CRABP and their biological potency. The action of RA through the mediation of CRABP may cause a hormone-like effect involving induction and/or depression of gene activity. An early cellular event in RA action will be the entry of the circulating retinoid into the cytoplasm and formation of a complex with the binding protein.