alpha-Taxilin is a novel binding partner of the syntaxin family, which is implicated in intracellular vesicle traffic. We have here found that alpha-taxilin interacts with the nascent polypeptide-associated complex (NAC), which is involved in transferring growing nascent polypeptide chains to appropriate co-translationally acting factors. NAC is composed of two subunits, alpha- and betaNACs. Both these subunits bound to alpha-taxilin through its C-terminal coiled-coil region in dose-dependent and saturable manners. The interactions of alpha-taxilin with alphaNAC and NAC but not with betaNAC were inhibited by syntaxin-4, indicating that alpha-taxilin binds to NAC mainly through its interaction with alphaNAC. When alphaNAC was over-expressed in COS-7 cells, alphaNAC was distributed in the cytosol and nucleus. However, co-expression of the alpha-taxilin fragment containing the alphaNAC-binding region eliminated the nuclear distribution of over-expressed alphaNAC. Moreover, other taxilin family members, beta- and gamma-taxilins, also bound to alphaNAC and thereby affected the nuclear distribution of over-expressed alphaNAC. Taken together with the evidence that alphaNAC functions in the nucleus as a transcriptional coactivator, our results raise the possibility that the taxilin family is involved not only in the translational process through its interaction with NAC but also in the transcriptional process through its interaction with alphaNAC alone.