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: J Yamauchi, T Iwamoto, S Kida, S Masushige, K Yamada, T Esashi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 285 Issue 2 Pg. 295-9 (Jul 13 2001) ISSN: 0006-291X [Print] United States
• PMID: 11444841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Carrier Proteins
• Ligands
• Lipoproteins
• Recombinant Proteins
• SEC14L2 protein, human
• Trans-Activators
• Transcription Factors
• Vitamin E
• Luciferases

Topics

• Amino Acid Sequence
• Animals
• Binding, Competitive
• COS Cells
• Carrier Proteins
• Cell Line
• Cell Nucleus (metabolism)
• Chlorocebus aethiops
• Cloning, Molecular
• Genes, Reporter
• Humans
• Kinetics
• Ligands
• Lipoproteins
• Luciferases (genetics)
• Molecular Sequence Data
• Open Reading Frames
• Recombinant Proteins (chemistry, metabolism)
• Restriction Mapping
• Sequence Alignment
• Sequence Homology, Amino Acid
• Stereoisomerism
• Substrate Specificity
• Trans-Activators (chemistry, genetics, metabolism)
• Transcription Factors (genetics, metabolism)
• Transfection
• Vitamin E (analogs & derivatives, chemistry, metabolism)