Elucidation of the mechanism of nuclear signal transduction by retinoic acid based on new insight and its applications

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Vitamin A is a micronutrient that is indispensable to maintaining health. The free acid (retinoic acid, RA) is an active form of vitamin A that elicits a wide variety of actions which are important to the body. It has attracted considerable attention from the viewpoint of prevention and treatment of cancers and neurological diseases etc. In the current study, retinoylation (protein post-translational modification by RA) was found to be a new RA mechanism of action that is not dependent on nuclear receptors. These findings resulted from detailed investigations using the human promyelocytic leukemia cell line HL60, which is differentiated by RA. New signal transmission mechanisms were analyzed that resulted in the identification of new RA-binding target proteins in the nucleus as well as proteins phosphorylated by retinoylated nuclear protein kinase A. These studies have clarified protein modifications that are associated with the actions of vitamin A.