Metabolism of retinoic acid: Implications for development and cancer

Vitamin A derived retinoids, including all-trans retinoic acid (RA), play a n important role in regulating cellular growth and differentiation. Biologi cal activities of retinoids are mediated through interactions with two clas ses of nuclear receptors, RA receptors (RARs) and retinoid X receptors (RXR s). In addition, cellular retinoid-binding proteins (CRBPs and CRABPs) and RA-metabolizing enzymes may explain the pleiotropic effects of retinoids. R ecently, a novel cytochrome P450 enzyme (CYP26) with specific RA 4-hydroxyl ase activity, which is rapidly induced by RA, has been cloned form man, mus e and zebra fish, fulfilling all requirements of an enzyme which could be o f crucial importance in controlling steady-state levels of active retinoids in cells and target tissues, thus protecting against excessive exposure. B esides 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.