MVP and vaults: a role in the radiation response

Abstract

Vaults are evolutionary highly conserved ribonucleoproteins particles with a hollow barrel-like structure. The main component of vaults represents the 110 kDa major vault protein (MVP), whereas two minor vaults proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (vPARP) and the 240 kDa telomerase-associated protein-1 (TEP-1). Additionally, at least one small and untranslated RNA is found as a constitutive component. MVP seems to play an important role in the development of multidrug resistance. This particle has also been implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses. Vaults are considered a prognostic marker for different cancer types. The level of MVP expression predicts the clinical outcome after chemotherapy in different tumour types. Recently, new roles have been assigned to MVP and vaults including the association with the insulin-like growth factor-1, hypoxia-inducible factor-1alpha, and the two major DNA double-strand break repair machineries: non-homologous endjoining and homologous recombination. Furthermore, MVP has been proposed as a useful prognostic factor associated with radiotherapy resistance. Here, we review these novel actions of vaults and discuss a putative role of MVP and vaults in the response to radiotherapy.

Figure 1

Overall structure of the vault shell. One molecule of MVP is colored in tan, and the others are colored in purple. (Left) Side view of the ribbon representation. The whole vault shell comprises a 78-oligomer polymer of MVP molecules. The size of the whole particle is ~670 Å from the top to the bottom and ~400 Å in maximum diameter. The particle has two protruding caps, two shoulders, and a body with an invaginated waist. Two half-vaults are associated at the waist with N-terminal domains of MVP. (Right) Top view of the ribbon representation. The maximum diameter of the cap is ~200 Å. The outer and the inner diameters of the cap-ring are shown. Figure reproduced from Tanaka et al. (2009) with permission from The American Association for the Advancement of Science (Sciences Magazine).