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 (alpha, beta, gamma, and delta) 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 alpha -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 alpha -tocopherol associated protein, TAP, which displays significant sequence similarity to the alpha -tocopherol transfer protein. Ligand competition analysis showed that recombinant TAP binds to alpha -tocopherol but not to other isomers of tocopherols. Using GFP fusion protein expression system, we ob served that TAP translocates from cytosol to nuclei in alpha -tocopherol-dependent fashion. Transient transfection experiment showed that TAP activates transcription of the reporter gene in alpha -tocopherol-dependent manner, These results suggest that the biological function of alpha -tocopherol is not only as an antioxidant but also as a transcriptional regulator of gene expression via association with a transcription factor TAP. (C) 2001 Academic Press.