Tocopherol-Associated Protein Is a Ligand-Dependent Transcriptional Activator

Vitamin E is a term that encompasses a group of potent, lipid-soluble, chain-breaking antioxidants. Structural analysis reveals that molecules having vitamin E activity include four isomers (α, β, γ, and δ) of both tocopherols and tocotrienols. Alpha-tocopherol has been shown to have the highest biological vitamin E activity in mammalian tissues based on fetal resorption assays, and it reverses vitamin E deficiency symptoms. Although the molecular functions fulfilled specifically by α-tocopherol have yet to be fully described, it is unlikely that they are limited to general antioxidant functions. Here we show the functional characterization of α-tocopherol associated protein, TAP, which displays significant sequence similarity to the α-tocopherol transfer protein. Ligand competition analysis showed that recombinant TAP binds to α-tocopherol but not to other isomers of tocopherols. Using GFP fusion protein expression system, we observed that TAP translocates from cytosol to nuclei in α-tocopherol-dependent fashion. Transient transfection experiment showed that TAP activates transcription of the reporter gene in α-tocopherol-dependent manner. These results suggest that the biological function of α-tocopherol is not only as an antioxidant but also as a transcriptional regulator of gene expression via association with a transcription factor TAP.