Metabolism of retinoic acid: implications for development and cancer

Vitamin A derived retinoids, including all-trans retinoic acid (RA), play an important role in regulating cellular growth and differentiation. Biological activities of retinoids are mediated through interactions with two classes of nuclear receptors, RA receptors (RARs) and retinoid X receptors (RXRs). In addition, cellular retinoid-binding proteins (CRBPs and CRABPs) and RA-metabolizing enzymes may explain the pleiotropic effects of retinoids. Recently, a novel cytochrome P450 enzyme (CYP26) with specific RA 4-hydroxylase activity, which is rapidly induced by RA, has been cloned from man, mouse and zebra fish, fullfilling all requirements of an enzyme which could be of crucial importance in controlling steady-state levels of active retinoids in cells and target tissues, thus protecting against excessive exposure. Besides the putative role of this newly identified CYP26 in contributing to susceptibility of cancer cells to retinoids, the possible function of this gene in early embryonic development is discussed.