Lipid soluble vitamins in gene regulation

Vitamin A (retinol) and vitamin D are lipid soluble vitamins that are precursors of the nuclear hormones all-trans retinoic acid (RA) and 1 alpha,25-dihydroxyvitamin D-3 (VD) that bind with high affinity to their cognate nuclear receptors, referred to as retinoic acid receptor (RAR) and vitamin D receptor (VDR). Both types of nuclear receptors are structurally related and belong to the same subclass of the nuclear receptor superfamily, a large family of ligand-inducible transcription factors. Both RAR and VDR form heterodimers preferentially with the nuclear receptor for 9-cis RA, referred to as the retinoid X receptor (RXR), but functional RAR-VDR heterodimers have also been observed. Moreover, both types of nuclear receptors interact in a ligand-dependent fashion with members of the same class of co-activator, co-repressor and co-integrator proteins. These similar molecular mechanisms of action provide several possibilities for an interaction of RARs with VDR that are all based on allosteric protein-protein interactions. These interactions can result in either an additive or a transrepressive functional interference between RA and VD. The two remaining lipid soluble vitamins, vitamins E and K, are not known to interact with nuclear receptors, but their structure does not exclude this possibility. Moreover, for vitamin E modulatory effects on transcription factors, such as AP-1, have been described. This review will discuss briefly gene regulation by the four lipid soluble vitamins.