Identification of a Novel Cytosolic Tocopherol‐Binding Protein: Structure, Specificity, and Tissue Distribution

Abstract

alpha‐Tocopherol plays an important role as a lipid‐soluble antioxidant. It is present in all major mammalian cell types and shows tissue‐specific distribution. This suggests the presence of specific proteins involved in intracellular distribution or metabolism of alpha‐tocopherol. A diminution of tocopherol plasma concentrations contributes to the development of diseases such as vitamin E deficiency (AVED), atherosclerosis, and prostate cancer. Further evidence has been obtained for the existence of sites in cellular metabolism and signal transduction where alpha‐tocopherol potentially plays a regulatory role. A signal transduction modulation specific for alpha‐tocopherol has been described in several model systems. Using radioactively labeled alpha‐tocopherol as tracer, we have isolated a new alpha‐tocopherol‐associated protein (TAP) from bovine liver. This protein has a molecular mass of 46 kDa and an isoelectric point of 8.1. From its partial amino acid sequence, a human gene has been identified with high homology to the newly described protein. Sequence analysis has established that the new TAP has structural motifs suggesting its belonging to a family of hydrophobic ligand‐binding proteins (RALBP, CRALBP,alpha‐TTP, SEC 14, PTN 9, RSEC 45). Human TAP has been cloned into Escherichia coli, and its tissue‐specific expression has been assessed by Northern blot analysis.