title: Tocopherol-associated protein is a ligand-dependent transcriptional activator.
abstract: 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 observed 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.
authors.affiliation: Division of Applied Food Research, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjyuku, Japan. junyama@nih.go.jp
authors.forename: J
authors.initials: J
authors.lastname: Yamauchi
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.forename: S
authors.initials: S
authors.lastname: Kida
authors.forename: S
authors.initials: S
authors.lastname: Masushige
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Esashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D002352:Carrier Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017930:Genes, Reporter; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008074:Lipoproteins; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism; D013379:Substrate Specificity; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D008074:Lipoproteins; D011994:Recombinant Proteins; C432422:SEC14L2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D014810:Vitamin E; D008156:Luciferases