The major vault protein is responsive to and interferes with interferon - - mediated STAT 1 signals

Introduction The 110 kDa major vault protein (MVP) represents the main component of evolutionary highly conserved ribonucleoprotein particles called vaults and accounts for 70% of the total particle mass (Mossink et al., 2003). Vaults are barrel-shaped structures with a hollow interior. They are composed of multiple copies of three proteins and small, untranslated vault RNAs. Vaults were found in species as diverse as the slime mold Dictyostelium discoideum, electric ray, sea urchin and mammals, pointing towards essential cellular functions of vaults especially in multicellular organisms. The localization of vaults in mammalian cells is mainly cytoplasmic, however, a small portion was also found to be associated with the nuclear membrane (Chugani et al., 1993). Vaults are present in a wide range of cell types at numbers of over 10 4 particles per cell (Kickhoefer et al., 1998). Although the precise function of this highly conserved structure has yet to be determined, vault morphology suggests a role in transport and sequestration processes of xenobiotics and/or cellular molecules (Suprenant, 2002). Vaults are generally present at notably high levels in tissues chronically exposed to xenobiotics, and MVP was also found to be overexpressed in certain tumor types when compared with their normal counterpart (Berger et al., 2001; Izquierdo et al., 1996; Zurita et al., 2003). For example, low levels of MVP were detected in normal human astrocytes, whereas all astrocytic brain tumors, including low-grade astrocytomas, expressed